Dual release dosage form capsule and methods, devices and systems for making same

ABSTRACT

Provided is a dual dosage form capsule, methods for producing and systems for making the same, which can provide dual release of the two dosages. The dual dosage form capsule has a first capsule member containing a first fill material and a second capsule member containing a second fill material. A band couples the first capsule member to the second capsule member and forms a third chamber defined by an inner surface of the band and each cap of the capsule members. An aperture allows fluid into the third chamber causing the band to at least partially dissolve so that the caps of the capsule members are exposed. The caps of the capsule members can dissolve at the same or different rates to control the timing of the release of the first and second fill materials and hence an active ingredient included within the fill material.

RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application62/530,658, filed Jul. 10, 2017, the entirety of which is incorporatedherein by reference.

TECHNICAL FIELD

The present disclosure relates generally to the field of capsules, andin particular a dual release dosage form capsule. The present disclosurealso relates to methods, devices and systems for manufacturing dualrelease dosage capsules.

BACKGROUND

Conventional capsules for pharmaceuticals or other powdered, granular orliquid substances, are two-piece capsules having telescoping bodies. Forexample, the bodies are generally tubular-shaped having a closed end andan open end. One body is generally larger than the diameter of the otherbody so that the open end of the larger body can at least partially beslipped over the smaller diameter body. The bodies can be tightlyfitted, for example, so that the fill material inside the capsule doesnot leak out. In some capsules a band may be used to secure the twobodies together.

While such two-piece capsules are known, the design of the conventionaltwo-piece capsule has several limitations and disadvantages. In liquidfilled capsules, for example, the cavity within the capsule can includeonly a single mixture. Hence, different active ingredients that interactwith each other, for example, cannot be included within the samecapsule. In other words, the capsule is limited to the delivery of onlyinternally compatible ingredients. Further, the contents of theconventional capsule are released at once when the capsule dissolves.Hence, there is no way to alter or modify the release time of the sameor different drugs. There are also limited ways to mix incompatibleingredients.

To address these issues, others have developed dosage form capsules thathave at least one smaller capsule stored within (inside) a largercapsule. Generally, such capsules require a larger two-piece capsuleforming the outer shell of the dosage form and one or more smallercapsules therein storing different mediums. Disadvantages of thisarrangement include size limitations of the capsules. For example, theinner capsule has a smaller volume than the outer capsule. Further, theouter capsule can be difficult to swallow if its volume is too large. Itcan also be difficult to manufacture the capsule-within-a-capsuledesign. Other attempts to address the limitations of the conventionaltwo-piece capsule include the use of solid particles that are dispersedwithin a liquid capsule fill. The particles, for example, may be coatedwith one or more substances to protect them from the liquid componentand/or to alter their release rate. Among other limitations, however,such solid/liquid fills are inherently expensive to manufacture.Further, not all drugs are available in solid form and/or amenable tocoating.

Therefore, there remains a need for a capsule that overcomes theproblems of the conventional capsule. More particularly, there remains aneed for a dosage form capsule that provides a dual release of the sameor different fill materials at the same and/or different times. Therefurther remains a need for a dosage form capsule that permits thedelivery of otherwise incompatible fill materials and activeingredients. There also remains a need for a dual release dosage formcapsule that simplifies assembly and filling processes of the capsule.

SUMMARY

In all aspects described herein, a dual dosage form capsule is provided,which may be a dual release capsule. The dual dosage form capsule has afirst end or capsule member filled with a first fill material and asecond end or capsule member filled with a second fill material, whichmay be the same or different materials. A first end of a band isconnected to the first capsule member to sealingly contain the firstfill material therein and an opposing second end connected to the secondcapsule member to sealingly contain the second fill material therein.This construction defines an internal chamber between the first capsulemember and the second capsule member within the band. The band includesone or more apertures therethrough radially oriented relative to alongitudinal axis of the capsule, thereby placing the internal chamberin fluid communication with the environment outside the capsule.

In multiple embodiments, the first end of the annular band is open andhas an end of the first capsule member received therein and the secondend of the annular band is open and has an end of the second capsulemember received therein. The end of the first capsule member received inthe annular band has a cap sealingly closing the end of the firstcapsule member and the cap is seated within the band, and the end of thesecond capsule member received in the annular band has a cap sealinglyclosing the end of the second capsule member and the cap is seatedwithin the band.

In another embodiment, the first end of the annular band is open and hasan end of the first capsule member received therein and the second endof the annular band is open and has an end of the second capsule memberreceived therein. Here, the annular band includes a cover therein forsealingly closing the end of the second capsule member and an openopposing end receiving the end of the first capsule member, which issealingly closed by a cap. Alternately, the band can be a two-partconstruction, a first annular band portion having a cover for the firstcapsule member integral therewith and a second annular band portionhaving a cover for the second capsule member integral therewith. Thefirst annular band portion and the second annular band portion each havean open end opposite the cover therein and the open ends are connectableto one another to form the band and either or both have the plurality ofapertures therethrough. An in yet another embodiment, the annular bandincludes a cover therein for sealingly closing the end of the secondcapsule member and for sealingly closing the end of the first capsulemember.

In other embodiments, the first end of the annular band is received inan open end of the first capsule member and the second end of theannular band is received in an open end of the second capsule member.Here, the annular band includes a cover therein for sealingly closingthe end of the second capsule member and for sealingly closing the endof the first capsule member. Alternately, the band can be a two-partconstruction, a first annular band portion having a cover for the firstcapsule member integral therewith and a second annular band portionhaving a cover for the second capsule member integral therewith. Thefirst annular band portion and the second annular band portion each havean open end opposite the cover therein and the open ends are connectableto one another to form the band and either or both have the plurality ofapertures therethrough.

In certain example embodiments, the dual release dosage form capsuleincludes a first capsule member having a first fill material and asecond capsule member having a second fill material. A band couples thefirst capsule member to the second capsule member and forms a thirdchamber defined by an inner surface of the band and a cap of the capsulemembers. An aperture in the band places the third chamber in fluidcommunication with the environment outside of the capsule. When thecapsule is swallowed, for example, digestive fluid can enter the thirdchamber through the aperture, thereby exposing the capsule members tothe fluid. In certain aspects, fluid movement into the third chambercauses the band to at least partially dissolve so that caps of thecapsule members are exposed.

In all aspects, the first fill material and the second fill material canbe released from the capsule at different times, thus enabling a dualtiming release of the fill materials or can be released from the capsuleat substantially the same time enabling the first and second fillmaterials to interact for the first time upon being released from thecapsule.

In certain example aspects described herein, a process for manufacturinga dual release dosage form capsule is provided, including devices andsystems for making the dual release dosage capsules described herein.The process for manufacturing a dual release dosage form capsuleincludes providing materials to a capsule body filling device that isconfigured to fill and seal fill materials into a shell body to form asealed capsule member. In another aspect, the process for manufacturinga dual release dosage form capsule includes providing sealed capsulemembers and/or a combination of a capsule member and a shell body to acapsule forming device. The capsule forming device can be sized andconfigured to couple two capsule members together with a band to formthe capsule.

The capsule forming machine has superimposed upper and lower plates thatare each rotatable about an axis of rotation. Each of the upper andlower plates define a plurality of voids for receiving a shell body or acapsule member of a capsule and the plurality of voids are positioned todefine a plurality of stations. A first distribution device isoperatively positioned at one of the plurality of stations of each ofthe upper and lower plates. An actuator is operatively connected toeither of the upper or lower plates and lifts and lowers the upper orlower plate relative to the other plate and/or pivots the upper or lowerplate relative to the other plate transverse to the rotational axis tomove a capsule assembly station thereof toward to the other plater andthen away from the other plate at predetermined times. The firstdistribution device distributes shell bodies or capsule members to afirst station. In all aspects, a second distribution device distributesa fill material when the first distribution device distributes shellbodies or distributes bands when the first distribution devicedistributes capsules members having a cap sealing enclosing a fillmaterial therein. In one embodiment, the first distribution device ofthe lower plate distributes first capsules members having a first bandportion sealing enclosing a first fill material therein and the firstdistribution device of the upper plate distributes second capsulemembers having a second band portion sealing enclosing a second fillmaterial therein, and at the capsule assembly station the first bandportion and the second band portion are mated together to form acapsule. The machine also includes a sealing device operativelypositioned at either the capsule assembly station or a stationsubsequent to the capsule assembly station.

A method of providing a dual release of one or more active ingredientsis provided. The method includes exposing the dual release dosage formcapsule describe herein to a fluid. Upon exposure to the fluid, a firstrelease of at least a portion of the first fill material occurs from thedual release dosage form capsule before a second release of at least aportion of the second fill material. Similarly, a method of providing adual release of one or more active ingredients in a subject is providedas described herein. The method includes, for example, administering tothe subject the dual release dosage form capsule described herein, suchas by oral consumption. Such administration of the dual release dosageform capsule results in a first release of at least a portion of thefirst fill material from the dual release dosage form capsule before asecond release of at least a portion of the second fill material. Thesecond release occurs at least one hour after the first release.

These and other aspects, objects, features, and advantages of theexample embodiments will become apparent to those having ordinary skillin the art upon consideration of the following detailed description ofillustrated example embodiments. Related methods of operation are alsoprovided. Other apparatuses, methods, systems, features, and advantagesof the dual release dosage form capsule, and process for making thecapsule, will be or become apparent to one with skill in the art uponexamination of the following figures and detailed description. It isintended that all such additional apparatuses, methods, systems,features, and advantages be included within this description, be withinthe scope of dual release dosage form capsule, and process for makingthe capsule, be protected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of a dual release dosage form capsule, inaccordance with certain example embodiments.

FIG. 2 is a side view of a dual release dosage form capsule having aplurality of apertures in the band, in accordance with certain exampleembodiments.

FIG. 3 is an exploded view of the capsule of FIG. 2, in accordance withcertain example embodiments.

FIG. 4 is cross-sectional view of an example capsule, illustrating theprofile taken through the line 4-4 as shown in FIG. 2, in accordancewith certain example embodiments.

FIG. 5A is a cross-sectional view of one embodiment of a band that canreceive a cap or a cap and capsule member.

FIG. 5B is a cross-sectional exploded view of the band of FIG. 5A havingreceived a cap and about to receive a first and second capsule member.

FIG. 6 is a cross-sectional view of the assembled capsule of FIG. 5B.

FIG. 7 is a cross-sectional assembled view of an inside fit for the endsof a band that is similar to the band of FIG. 5A.

FIG. 8 is a cross-sectional partial assembled view of a capsule havinglids integral with annular band portions that are mateable to oneanother to form the band.

FIG. 9 is a schematic view of a capsule body filling device formanufacturing a dual release dosage form capsule.

FIG. 10 is a schematic view of a capsule forming device formanufacturing a dual release dosage form capsule.

FIG. 11 is an enlarge partial view in a longitudinal cross-sectionthrough the capsule assembly station of a capsule forming device.

FIG. 12 is a schematic view of first and second rotating plates of thecapsule forming device of FIG. 10, in accordance with certain exampleembodiments.

FIG. 13 is a schematic view of first and second rotating plates ofanother embodiment of a capsule forming device of FIG. 10.

DETAILED DESCRIPTION

Provided herein is a dual release dosage form capsule, along with aprocess for manufacturing the dual release dosage form capsule. The dualdosage form capsule includes two capsule halves, each of which arecapped on one end to form a capsule member. Each capsule member, forexample, can be filled with a different fill material. A band is used tocouple the two capsule members together, thereby forming the dual dosageform capsule. Application of the band to the capsule members forms achamber between the capsule members, the chamber being contiguous withthe exterior surfaces of the capsule member caps and the interiorsurface of the band. The band includes one or more apertures, thusexposing the third chamber to the environment. The apertures, forexample, permit fluid movement into the chamber between the capsulemembers, thereby facilitating release of the fill materials in apredetermined fashion.

More particularly, in certain examples the caps of each capsule membercan be made of different materials, such as materials that dissolve atdifferent rates. Additionally or alternatively, the caps can beconfigured differently so that they dissolve at different rates, therebyreleasing the fill material at different rates. For example, one cap maybe thicker than the cap of the other capsule member, thus increasing thedissolve time for the thicker cap and hence delaying the release of theactive ingredient covered by the thicker cap. The thickness of the capmay be in a range from 0.25 mm to 1.5 mm, more preferably 0.5 mm to 1mm.

In all embodiments, the band is also made of a dissolvable material,such that the band also dissolves when the dual dosage form capsule isswallowed and exposed to digestive fluids. In particular, the aperturesact as perforations in the band to provide a point of weakness uponwhich the digestive fluids will act to divide the capsule in half and/orenable digestive fluids access to the caps.

These and other features of the dual release dosage form capsuleadvantageously permit the timed release of active ingredients from asingle dosage form. That is, the dual release capsule described hereinallows a dual timing release so that a first fill material positioned ina portion of the capsule can be released at a different time than asecond fill material positioned in a second portion of the capsule. Forexample, a first pharmaceutical, such as ibuprofen, can be positioned inthe capsule and released at a first time, and a second pharmaceutical,such as acetaminophen, can be positioned in the capsule and released ata second time that is different than the first time. When the capsule isingested, the ibuprofen and acetaminophen are thus released at differenttimes. Hence, in this example, a longer duration of pain management canbe achieved from a single dosage form, as compared to taking ibuprofenor acetaminophen alone in separate dosage forms. The dosage form, forexample, can be a modified release dosage form, a sustained releasedosage form, a controlled-release dosage form, or extended releasedosage form.

In certain examples, the dual release capsule described herein allows asubstantially simultaneous release of at least two fill materials, thefill materials otherwise being generally incompatible if mixed together.For example, if two pharmaceutical agents undesirably interact therebyshortening shelf life, a first pharmaceutical agent can be positioned ina first portion of the dual release dosage form and a secondpharmaceutical agent can be positioned in a separate, second portion ofthe dosage form. In this example, the first and second pharmaceuticalagents can be released from the capsule at substantially the same time,such as when ingested, but otherwise maintained separately beforeingestion. Hence, in certain examples the dual dosage form describedherein advantageously increases shelf life.

The dual release dosage capsule form can be made in a variety of ways.In certain examples, the capsule members can be formed separately andthen joined together with a band. For example, a capsule body fillingdevice can be used to fill the capsule halves and to form the twocapsule members by application of a cap to each capsule halve. A capsuleforming device can then be used to couple the capsule members togetherwith the band, thereby forming the dual release dosage form capsuledescribed herein. The band, for example, can be a pre-formed band thatincludes one or more apertures.

The invention will now be described in detail by way of reference onlyusing the following definitions and examples. All patents andpublications referred to herein are expressly incorporated by referencein their entirety. It is to be understood that one, some or all of theproperties of the various embodiments described herein may be combinedto form other embodiments of the present invention. Further, the sectionheadings used herein are for organizational purposes only and are not tobe construed as limiting the subject matter described.

The terms used herein generally have their ordinary meanings in the art,within the context of the disclosure, and in the specific context whereeach term is used. Certain terms that are used to describe thedisclosure are discussed below, or elsewhere in the specification, toprovide additional guidance to the practitioner regarding thedescription of the disclosure. For convenience, certain terms arehighlighted in quotation marks. The use of such highlighting has noinfluence on the scope and meaning of a term. Rather, the scope andmeaning of a term is the same, in the same context, whether or not it ishighlighted.

It will be appreciated that the same thing can be said in more than oneway. Hence, alternative language and synonyms can be used for any one ormore of the terms discussed herein. Nor is any special significance tobe placed upon whether or not a term is elaborated or discussed herein.Synonyms for certain terms can also be provided herein. A recital of oneor more synonyms does not exclude the use of other synonyms, forexample. The use of examples anywhere in this specification includingexamples of any terms discussed herein is illustrative only and is notintended to further limit the scope and meaning of the disclosure or ofany exemplified term. Likewise, the disclosure is not limited to variousembodiments given in this specification.

As used herein, the singular forms “a,” “an” and “the” include pluralreferents unless the context clearly dictates otherwise. Thus, forexample, reference to a “capsule” includes aspects having two or morecapsules unless the context clearly indicates otherwise.

Ranges can be expressed herein as from “about” one particular value,and/or to “about” another particular value. “About” as used herein meansplus or minus 5% of a numerical value. When such a range is expressed,another aspect includes from the one particular value and/or to theother particular value. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular value forms another aspect. It will be furtherunderstood that the endpoints of each of the ranges are significant bothin relation to the other endpoint, and independently of the otherendpoint.

As used herein, the terms “optional” or “optionally” mean that thesubsequently described event or circumstance can or cannot occur, andthat the description includes instances where said event or circumstanceoccurs and instances where it does not.

As used herein, a “capsule” refers to a pharmaceutical device having atleast one body and at least one cap that can be coupled together todefine at least one chamber for a dosage. In certain exampleembodiments, the capsule includes a liquid fill, such as a suspension orsemisolid, a powder fill and/or a granular fill which is positioned inthe chamber to form a single, hermitically sealed dosage form. As oneskilled in the art will appreciate, any portion of the capsule can becomposed of gelatin, a plasticizer, and water, and can also includeother ingredients such as preservatives, coloring, flavorings,opacifying agents, sweetening agents, acids, salts, medicaments, orother agents to achieve a desired dosage effect.

As used herein, a “subject” refers to a vertebrate. The vertebrate maybe a mammal, for example, a human. The subject may be a human patient. Asubject may be a patient suffering from or suspected of suffering from adisease or condition and may be in need of treatment or diagnosis or maybe in need of monitoring for the progression of the disease orcondition. The patient may also be on a treatment therapy that needs tobe monitored for efficacy.

As used herein, “pharmaceutically acceptable salts” refer to derivativesof a given compound, such as an active ingredient, wherein thetherapeutic compound is modified by making acid or base salts thereof.The pharmaceutically acceptable salts include the conventional non-toxicsalts, for example, from non-toxic inorganic or organic acids. Forexample, such conventional non-toxic salts include those derived frominorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfonic,sulfamic, phosphoric, nitric and the like; and the salts prepared fromorganic acids such as amino acids, acetic, propionic, succinic,glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic,maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic,sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic,ethane disulfonic, oxalic, isethionic, and others known to those ofordinary skill in the art. For acidic compounds, the salt may include anamine-based (primary, secondary, tertiary or quaternary amine) counterion, an alkali metal cation, or a metal cation. Lists of suitable saltsare found in texts such as Remington's Pharmaceutical Sciences, 18th Ed.(Alfonso R. Gennaro, ed.; Mack Publishing Company, Easton, Pa., 1990);Remington: the Science and Practice of Pharmacy 19th Ed. (Lippincott,Williams & Wilkins, 1995); Handbook of Pharmaceutical Excipients, 3rdEd. (Arthur H. Kibbe, ed.; Amer. Pharmaceutical Assoc., 1999); thePharmaceutical Codex: Principles and Practice of Pharmaceutics 12th Ed.(Walter Lund ed.; Pharmaceutical Press, London, 1994); The United StatesPharmacopeia: The National Formulary (United States PharmacopeialConvention); and Goodman and Gilman's: the Pharmacological Basis ofTherapeutics (Louis S. Goodman and Lee E. Limbird, eds.; McGraw Hill,1992), the disclosures of which are hereby incorporated by reference intheir entirety. As used herein, an active ingredient can include apharmaceutically acceptable salt of the active ingredient.

As used herein, a “probiotic” generally means live bacteria (also calledmicroflora or microorganisms) that confer a beneficial effect when aneffective amount is introduced into the intestinal tract of a mammal.

“Prebiotic” means any substance that can be consumed by a relevantprobiotic, or that otherwise assists in keeping the relevant probioticalive or stimulates its growth, and includes mucopolysaccharides,oligosaccharides, polysaccharides, amino acids, vitamins, nutrientprecursors and proteins. “Compliment” or “complimentary” with respect toa prebiotic means that the prebiotic is consumed by, or otherwiseassists in keeping alive or stimulates the growth of, a relevantprobiotic.

Example Embodiments

The following description and drawings are illustrative and are not tobe construed as limiting. Numerous specific details are described toprovide a thorough understanding of the disclosure. However, in certaininstances, well-known or conventional details are not described in orderto avoid obscuring the description. References to one or an embodimentin the present disclosure can be, but not necessarily, are references tothe same embodiment. And, such references mean at least one of theembodiments.

Further, reference to an “embodiment” or “example embodiment” means thata particular feature, structure, or characteristic described inconnection with the embodiment is included in at least one embodiment ofthe disclosure. Similarly, the appearance of the phrase “in certainembodiments” in various places herein are not necessarily all referringto the same embodiment, nor are separate or alternative embodimentsmutually exclusive of other embodiments. Moreover, various features aredescribed which can be exhibited by some embodiments and not by others.Similarly, various requirements are described which can be requirementsfor some embodiments but not other embodiments.

Dual Dosage Release Capsule

Turning to the drawings, FIGS. 1-3 are illustrations depicting exampledual dosage form capsules 10, in accordance with certain exampleembodiments, with or without a plurality of apertures in the band 3. Asshown, the capsule can include a first shell body 1 and an opposedsecond shell body 2. A first cap 7 can be sized and configured toenclose a first open end 11 of the first shell body, and a second cap 8can be sized and configured to enclose a second open end 21 of thesecond shell body. A band 3 can be coupled to the first shell body 1 andthe second shell body 2 to form the dual dosage form capsule 10.

The first shell body 1 includes the first open end 11, a first closedend 12 and a first sidewall 13 extending therebetween. The firstsidewall and the first closed end cooperate to define a first chamber 5,the first chamber being in fluid communication with the atmosphere viathe first open end. That is, the first chamber 5 of the first shell bodycan be accessible through the first open end 11. In another exampleembodiment, at least portions of the first closed end 12 and/or thefirst sidewall 13 can be arcuate in shape. For example, at least aportion of the first sidewall can be substantially cylindrical in shape,such that the first open end 11 is substantially circular in crosssection having a first end diameter. Of course, other shapes of thefirst open end, the first closed end, and the first sidewall arecontemplated.

Referring to FIGS. 3 and 4, the first cap 7 is sized and configured toclose the first open end 11 of the first shell body 1. In certainexample embodiments, the first cap 7 can include a first cover 14 havinga similar size and shape as the first open end. Optionally, the firstcover 14 can have a slightly larger size and/or shape than the firstopen end 11. For example, if the first open end is substantiallycircular having a first end diameter, the first cap 7 can besubstantially circular having a first cover diameter that is greaterthan or equal to the first end diameter. In another example embodiment,the first cover 14 can have an inner surface 18 configured to face thefirst chamber 5 when assembled and an opposed outer surface 19configured to face away from the first chamber when assembled.

A first lip 15 extends from the distal edge 16 of the first cover 14. Inone example embodiment, at least a portion of the first lip 15 canextend from the distal edge 16 of the first cover 14 at a substantiallyright angle relative to the first cover. Optionally, at least a portionof the first lip 15 can extend from the distal edge 16 of the firstcover 14 at an acute angle relative to the first cover. In use, anddescribed more fully below, at least a portion of the first cover 14and/or the first lip can engage a distal edge 17 of the first sidewall13 to seal a first fill material 36 (FIG. 4) in the first chamber 5 andform a first capsule member 20. For example, at least a portion of thefirst cover 14 and/or the first lip can frictionally engage the distaledge 17 of the first sidewall 13 to seal the first chamber and form thefirst capsule member. In another example embodiment, a laser or otherheat source can be directed to at least a portion of the first cover 14and/or the first lip to seal the first chamber 5 and form the firstcapsule member 20.

The second shell body 2 includes the second open end 21, a second closedend 22, and a second sidewall 23 extending therebetween. The secondsidewall and the second closed end can cooperate to define a secondchamber 6, the second chamber being in fluid communication with theatmosphere via the second open end. That is, the second chamber of thesecond shell body can be accessible through the second open end 21. Incertain example embodiments, at least portions of the second closed end22 and the second sidewall 23 can be arcuate in shape. For example, atleast a portion of the second sidewall can be substantially cylindricalin shape, such that the second open end 21 is substantially circular incross section having a second end diameter. Of course, other shapes ofthe second open end, the second closed end and the second sidewall arecontemplated. In a further embodiment, the second end diameter can beless than, substantially equal to, or greater than the first enddiameter.

The second cap 8 can be sized and configured to enclose the second openend 21 of the second shell body 2. In one example embodiment, the secondcap 8 can include a second cover 24 having a similar size and shape asthe second open end 21. Optionally, the second cover 24 can have aslightly larger size and/or shape than the second open end 21. Forexample, if the second open end 21 is substantially circular having asecond end diameter, the second cap 8 can be substantially circularhaving a second cover diameter that is greater than or equal to thesecond end diameter. In another example embodiment, the second coverdiameter can be less than, substantially equal to, or greater than thefirst cover diameter. In a further example embodiment, the second cover24 can have an inner surface 28 configured to face the second chamber 6when assembled and an opposed outer surface 29 configured to face awayfrom the second chamber when assembled.

A second lip 25 extends from a distal edge 26 of the second cover 24.For example, at least a portion of the second lip can extend from thedistal edge of the second cover at a substantially right angle relativeto the second cover 24. Optionally, at least a portion of the second lip25 can extend from the distal edge of the second cover at an acute anglerelative to the second cover 24. In use, described more fully below, atleast a portion of the second cover and/or the second lip can engage adistal edge 27 of the second sidewall 23 to seal a second fill material37 in the second chamber 6 and form a second capsule member 30. Forexample, at least a portion of the second cover 24 and/or the second lip25 can frictionally engage the distal edge 27 of the second sidewall 23to seal the chamber and form the second capsule member. In anotherexample embodiment, a laser or other heat source can be directed to atleast a portion of the second cover 24 and/or the second lip to seal thesecond chamber 6 and form the second capsule member 30.

As shown in FIGS. 1-4, the band 3 is an endless annular band includingan outer surface 31 having an outer diameter and an inner surface 32(labeled in FIG. 4) having an inner diameter. Thus, a passage 33 havinga first entry port 34 and an opposed second entry port 35 can be definedin and extend through the annular band. In all aspects, the innerdiameter of the band 3 can be substantially equal to, slightly greaterthan, or slightly smaller than at least one of the first end diameter ofthe first shell body 1, the first cover diameter of the first cap 7, thesecond end diameter of the second shell body 2, and the second coverdiameter of the second cap 8 to provide for an outside fit as shown inFIGS. 1-6 and 8 or an inside fit as shown in FIG. 7.

The band in any and/or all of these embodiments includes a snap-fit orclick-fit feature to connect the band to the first shell body 1 andsecond shell body 2, but it is not required to have this feature. InFIG. 4, the band 3 has a flange 38 at the periphery of the first endport 34 that extends radially inward toward the first shell body 1 andsnaps or clicks over the end of the first lip 15 of cap 7. Likewise, theband 3 has a flange 39 at the periphery of the second end port 35 thatextends radially inward toward the second shell body 2 and snaps orclicks over the end of the first lip 25 of cap 8. In FIG. 5A-6 each ofthe first shell body and second shell body 1, 2 have an exterior ridge61, 62 at the open ends thereof over which the flanges 58, 59 of band 43snap-fit or click-fit. And, in FIG. 7 each of the first shell body andthe second shell body 1, 2 have an interior ridge 63, 64 at the openends thereof over which flanges 58′, 59′ of the band 43′ snap-fit orclick-fit.

In any and all embodiments, at least one aperture 9, but preferably aplurality of apertures 9, can be defined in a portion of the band thatextends from the outer surface 31 of the band to the inner surface 32,thus allowing communication between the environment surrounding theouter surface 31 of the band 3 and the environment inside passage 33 ofthe band 3. In one embodiment, when a plurality of apertures 9 arepresent, the apertures are spaced equidistant apart around 9 the band ina plane transverse to the longitudinal axis along line 4-4 of FIG. 2,thereby forming a perforated ring in the band. In another embodiment,the plurality of apertures is positioned as two separate groups ofapertures in two different planes transverse to the longitudinal axis asshown in FIG. 8. While the illustration in FIG. 8 has the aperturesaligned with one another in the two planes, the apertures, may be offsetrelative to one another.

Referring now to FIGS. 5A-7, alternate embodiments for the band areillustrated in which one of the covers for the first or second shellbody 1, 2 is built into the band, i.e., is integral therewith to reducethe number of parts for the assembly process. Here the band 43 is anendless annular band having an outer surface 51 having an outer diameterand an inner surface 52 (labeled in FIG. 5A) having an inner diameter. Acover 47 spanning the inner diameter to sealingly close one of the firstor second shell bodies 1, 2, is integral within the band 43 at aposition more proximate a first end 44 thereof than a second end 45thereof. In the embodiment of FIGS. 5A-6, the first end 44 defines afirst entry port 54 and the second end 45 defines an opposed secondentry port 55 for ultimate receipt of the open ends of the first andsecond shell bodies 1, 2, respectively. The inner surface 52 of band 43includes a feature, such as ribs 48 or an annular shoulder (not shown),to define a seat for receipt of a cap 8. Cap 8 may be received in band43 alone and fixedly, sealingly connected thereto by any suitablemethods known or hereinafter developed as shown in FIG. 5B, or cap 8 maybe sealing connected to the second shell body 2, which is then receivedinto the band 43 as a unit as illustrated with dashed lines in FIG. 5A.

A plurality of apertures 9, as described above, are present in the band43 at a position between the cover 47 and the cap 8. Further, in theassembled state of FIGS. 5B and 6, an internal chamber 53 is definedbetween the cover 47 and the cap 8 and is in fluid communication withthe exterior environment through the plurality of apertures 9.

Referring now to FIG. 7, when the band is for an inside fit, it isdesignated 43′ and the cover 47 may be positioned within the band oralternately, the cover may be in the position of 47′ at and closing thefirst end 44 of the band shown with dashed lines in the drawing.Likewise, cap 8 may be positioned within the band or it may be in theposition 8′ at and closing the second end 45 of the band as shown withdashed lines in the drawing. The inner surface 52 of band 43′ includes afeature, such as ribs 48 or an annular shoulder (not shown), to define aseat for receipt of cap 8. Hereto, a plurality of apertures 9, asdescribed above, are present in the band 43′ at a position between thecover 47 and the cap 8 or cover 47′ and cap 8′. Further, an internalchamber 53 is defined between the cover 47 and the cap 8 or cover 47′and cap 8′ and is in fluid communication with the exterior environmentthrough the plurality of apertures 9.

Referring now to FIG. 8, the band may have a two-part construction 70where each annular band portion 71, 72 has a cover 74, 75, respectively,for sealingly closing a shell body integral therewith. The first annularband portion 71 and the second annular band portion 72 each have an openend 76, 77 opposite the cover 74, 75 therein and the open ends 76, 77are connectable to one another to form a band connecting the two halvesof the capsule into a complete capsule unit. The connection between thefirst and second annular band portions 71, 72 is illustrated as snap-fitor click-fit feature shown as an annular ridge 78 in the inside of theshell body 1 and defining the open end 76 and an annular groove 79 forreceiving the annular ridge 78 in the exterior surface of the secondannular band 72. The reverse configuration is also possible. Here, thefirst annular band portion 71 and/or the second annular band portion 72includes a plurality of apertures 9 therethrough radially orientedrelative to a longitudinal axis of the capsule, thereby placing aninternal chamber formed between the covers 74, 75 in the assembled statein fluid communication with the environment outside the capsule.

Referring back to FIG. 3, to form the first and second capsule members20, 30, a first predetermined amount of a first fill material 36 can beinserted through the first open end 11 of the first shell body 1 andinto the first chamber 5. The first cap 7 can be positioned over thefirst open end and at least a portion of the first cap 7 can be coupledto the first shell body to the form the first capsule member 20 havingthe first fill material 36 sealed inside the first chamber. For example,the first cap 7 can be positioned over the first open end 11 and atleast a portion of the first cap 7 can be heat sealed to the first shellbody 1 to the form the first capsule member 20 having the first fillmaterial 36 sealed inside the first chamber 5. Similarly, a secondpredetermined amount of a second fill material 37 can be insertedthrough the second open end 21 of the second shell body 2 and into thesecond chamber 6. The second cap 8 can be positioned over the secondopen end and at least a portion of the second cap can be coupled to thesecond shell body to form the second capsule member 30 having the secondfill material sealed inside the second chamber. For example, the secondcap 8 can be positioned over the second open end 21 and at least aportion of the second cap can be heat sealed to the second shell body 2to form the second capsule member 30 having the second fill material 37sealed inside the second chamber 6.

To form the capsule 10 of FIG. 1 or FIG. 2, the band 3 couples the firstcapsule member 20 to the second capsule member 30. As described morefully below, at least a portion of the first open end 11 (sealed withthe first cap 14) of the first shell body 1 is inserted through thefirst entry port 34 and into the passage 33 of the band. In one exampleembodiment, the first shell body can be positioned so that it passesthrough the first entry port but does not extend to the second entryport 35. That is, at least a portion of the first shell body 1 can bepositioned in the passage 33 without extending all the way through thepassage from the first entry port 34 to the second entry port 35.Similarly, at least a portion of the second open end 21 (sealed with thesecond cap 24) of the second shell body 2 can be inserted through thesecond entry port 35 and into the passage 33 of the band. In certainexample embodiments, the second shell body can be positioned so that itpasses through the second entry port 35 but does not extend to the firstentry port 34. That is, at least a portion of the second shell body 2can be positioned in the passage 33 without extending all the waythrough the passage from the second entry port 35 to the first entryport 34.

In the passage 33 of the band 3, the first capsule member 20 can bespaced from the second capsule member 30 a predetermined distance. Thepredetermined distance is a distance greater than zero such that a thirdchamber 4 or 33 (FIG. 4) is defined by the first capsule member 20, thesecond capsule member 30 and the inner surface 32 of the band 3. In suchexample embodiments, the apertures 9 defined in the band can place thethird chamber 4 in sealed fluid communication with theatmosphere/environment outside the capsule 10.

To form the capsule 10′ of FIG. 6 or capsule 10″ of FIG. 7, the band canbe coupled to the shell bodies 1 and 2 in various steps. In onevariation, according to FIG. 5A, the band 43 is mated to the open end ofthe first shell body 1 as an outside fit (FIG. 6) after being filledwith fill material. Cap 8 is sealingly connected to the open end of thesecond shell body 2 after being filled with fill material to form asecond capsule member 30. This second capsule member 30 is received inthe open end 55 of the band 43 to form capsule 10′. In another variationaccording to FIGS. 5A and 5B, a cap 8 is securely seated within the band43. The first shell body 1 is filled with fill material and the open endthereof is sealingly received within the band 43 to form a first capsuleunit. The second shell body 2 is filled with fill material and the openend of the first capsule unit formed by the band 43 is seated over theopen end of the second shell body 2 to sealingly close the second shellbody 2 and form the capsule 10′. In another variation, according to FIG.7, a cap 8 or 8′ is securely seated within band 43′. Then, the firstshell body 1 is filled with fill material and the open end thereofsealing receives a first end of the band 43′ therein to form a firstcapsule unit. The second shell body 2 is filled with fill material andthe open end thereof sealingly receives the second end of the band 43′therein to form capsule 10″.

To form a capsule from the first capsule member 20″ and the secondcapsule member 30″ of FIG. 8, the first shell body 1 is filled with fillmaterial and is sealingly mated to the first annular band portion 71with either an outside fit as shown or an inside fit as illustrated inFIG. 7. The second shell body 2 is filled with fill material and issealingly mated to the second annular band portion 72 with either anoutside fit as shown or an inside fit as illustrated in FIG. 7. Then,the first and second capsule members 20″ and 30″ are mated togetherusing the open ends 76, 77 of first and second annular band portions 71,72, thereby forming a complete capsule.

In all aspects, once the shell bodies, caps, bands, capsule members,etc. are in the desired positions to form a capsule, the band can besealed to the respective parts/members using known or hereinafterdeveloped techniques. For example, the band can be sealed with heat,such as a laser or an oven, with adhesives. In another example, the bandcan be friction fit to the shell bodies and/or have the snap-fit orclick-fit features described above.

In any of the embodiments disclosed herein, the first shell body 1, cap7, band 43, band 43′, and first annular band portion 71 can be formedfrom different materials than the second shell body 2, cap 8, cap 8′,and second annular band portion 72, so that these respective componentsdissolve at different rates. As an illustrative example the caps 7 and 8are discussed further below. These examples are equally applicable toany other combination of respective shell bodies, bands and caps andannular band portions. The first cap 7 of the first capsule member 20can be formed from a different material than the second cap 8 of thesecond capsule member 30 such that the caps dissolve at different rates,and thus, the contents of the respective first and second chambers 5, 6can be released at different times when the capsule is ingested. Assuch, the fill material of the first and second chambers 5, 6 can bereleased sequentially. For example, the first fill material 36 can bereleased near the time of ingestion, while the second fill material 37can be released minutes our hours later, such as 1, 2, 3, 4, 5, or 6hours after release of the first fill material 36. Allowing portions ofthe first capsule member 20 and the second capsule member 30 to bedissolved at different rates allows a dual timing release so that thefirst fill material 36 positioned in the first chamber 5 can be releasedfrom the first chamber at a different time than the second fill material37 positioned in the second chamber 6.

In any of the embodiments disclosed herein, the first shell body 1, cap7, band 43, band 43′, and first annular band portion 71 can be formedfrom the same or different materials than the second shell body 2, cap8, cap 8′, and second annular band portion 72, so that the capsulemembers dissolve at approximately the same rate. As an illustrativeexample the caps 7 and 8 are discussed further below. These examples areequally applicable to any other combination of respective shell bodies,bands and caps and annular band portions. For example, the first cap 7of the first capsule member 20 can be formed from the same material asthe second cap 8 of the second capsule member 30 such that the capsdissolve at substantially the same rate, and thus, the contents of therespective first and second chambers 5, 6 can be released atsubstantially the same time. Allowing portions of the first capsulemember 20 and the second capsule member 30 to be dissolved atsubstantially the same time allows a substantially simultaneous releaseof at least two fill materials. For example, if two pharmaceuticalagents undesirably interact during shelf life, such as when mixed, onepharmaceutical agent can be inserted into the first chamber 5 of thefirst capsule member 20, and a second pharmaceutical agent can beinserted into the second chamber 6 of the second capsule member. In suchexample embodiments, the first and second pharmaceutical agents wouldnot interact with each other until the substantially simultaneousrelease. In other example embodiments, the first and second materials36, 37 may be separated as described herein to both prevent anyundesirable interaction between the fill materials and to permitsequential release of the first and second fill materials as describedherein.

In use, the at least one aperture 9 in the band 3 can permit fluid toenter the third chamber 4, 33 such as digestive fluid when the dualrelease dosage form capsule is swallowed and enters the digestive tract.The digestive fluid can then contact the caps 7, 8, thereby dissolvingthe caps as described herein. In certain example embodiments, once a capis at least partially digested, the fill material within the capsulemember associated with at least partially dissolved cap can move intothe third chamber 4 and then out of the dosage form through the one ormore apertures 9 (and hence into the environment surrounding the dualrelease dosage form). Additionally or alternatively, in use the fluidentering the third chamber 4 can cause the band 3 to completely orpartially fall off of the capsule members 20, 30 so that the first cover14 of the first capsule member and the second cover 24 of the secondcapsule member are fully or partially exposed. In such exampleembodiments, the caps can then be dissolved when exposed to the fluid,such as digestive fluid. The capsule members can then release their fillmaterial in a substantially simultaneously manner, or in a dual timedmanner, as described herein.

Additionally or alternatively, in use the fluid entering the thirdchamber 4, 33 causes the band to at least partially dissolve so that thefirst cover of the first capsule member 20 and the second cover of thesecond capsule member 30 are at least partially exposed. The exposedcovers of the capsule members can then be dissolved, such as viadigestive fluid. If the first cap 7 is formed from a different materialthan the second cap 8 such that the caps dissolve at different rates,the contents of the respective first and second chambers 5, 6 can bereleased at different times. If the first cap 7 is formed from the samematerial as the second cap 8 such that the caps dissolve atsubstantially the same rate, the contents of the respective first andsecond chambers 5, 6 can be released at substantially the same time.

When a rapidly dissolving portion of the dual release dosage formcapsule is desired, such as a rapidly dissolving band and/or a cap (7 or8), the rapidly dissolving portion can be made from an inert andnon-toxic composition that is at least partially, and preferablysubstantially completely, soluble and/or erodible in an environment ofuse. For example, the rapidly dissolving portion will be soluble and/orerodible in aqueous environments such as, for example, the buccal cavityand/or upper GI tract, e.g., the stomach, duodenum, jejunum or uppersmall intestines. Exemplary materials are disclosed in U.S. Pat. Nos.4,576,604 and 4,673,405, and the text Pharmaceutical Dosage Forms:Tablets Volume I, Second Edition. (A. Lieberman. ed. 1989, MarcelDekker, Inc.), the relevant disclosures of which are hereby incorporatedby reference in their entirety. In certain example embodiments, therapidly dissolving portion of the dual release dosage form capsule 10will be substantially soluble (or erodible) in saliva, gastric juices,or acidic fluids.

According to the U.S. Department of Health and Human Services Food andDrug Administration Center for Drug Evaluation and Research (CDER), animmediate release drug product is considered rapidly dissolving when amean of 85 percent or more of the labeled amount of the drug substancedissolves within 30 minutes, using United States Pharmacopeia (USP)Apparatus 1 at 100 rpm or Apparatus 2 at 50 rpm (or at 75 rpm whenappropriately justified (see section III.C.) in a volume of 500 mL orless (or 900 mL when appropriately justified) in each of the followingmedia: (1) 0.1 N HCl or Simulated Gastric Fluid USP without enzymes; (2)a pH 4.5 buffer; and (3) a pH 6.8 buffer or Simulated Intestinal FluidUSP without enzymes. Further, an immediate release product is consideredvery rapidly dissolving when a mean of 85 percent or more of the labeledamount of the drug substance dissolves within 15 minutes, using theabove-mentioned conditions.

When a slowly dissolving portion of the dual release dosage form capsuleis desired, such as a slowly dissolving cap (7 or 8), the slowlydissolving portion can be made from several known digestion-resistantpolymer compositions, including those conventionally used for entericcoating. Such cap formulations, for example, provide a delayed andsustained release of fill material and can include materials that aresoluble or erodible in intestinal juices, substantially pH neutral orbasic fluids but for the most part insoluble in gastric juices or acidicfluids. A wide variety of polymeric materials are known to possess thesevarious solubility properties. Such polymeric materials include, forexample, cellulose acetate phthalate (CAP), cellulose acetatetrimelletate (CAT), poly(vinyl acetate) phthalate (PVAP), hydroxypropylmethylcellulose phthalate (HP), poly(methacrylate ethyl acrylate) (1:1)copolymer (MA-EA), poly(methacrylate methyl methacrylate) (1:1)copolymer (MA-MMA), poly(methacrylate methyl methacrylate) (1:2)copolymer, Eudragit L-30-D™ (MA-EA, 1:1), Eudragit™ L-100-55™ (MA-EA,1:1), hydroxypropyl methylcellulose acetate succinate (HPMCAS),Coateric™ (PVAP), Aquateric™ (CAP), AQUACOAT™ (HPMCAS) and combinationsthereof. The slow release cap, for example, can also include dissolutionaids, stability modifiers, and bioabsorption enhancers.

In certain example embodiments, the slowly dissolving portion of thedual release dosage form capsule, such as the slowly dissolving cap,includes hydroxypropylcellulose, microcrystalline cellulose (MCC,Avicel™ from FMC Corp.), poly (ethylene-vinyl acetate) (60:40) copolymer(EVAC from Aldrich Chemical Co.), 2-hydroxyethylmethacrylate (HEMA),MMA, terpolymers of HEMA: MMA:MA synthesized in the presence ofN,N′-bis(methacryloyloxyethyloxycarbonylamino)-azobenzene, azopolymers,enteric coated timed release system components (Time Clock® fromPharmaceutical Profiles, Ltd., UK) and/or calcium pectinate. In certainexample embodiments, a poly(vinylpyrrolidone)-vinyl acetate copolymer(e.g., material supplied by BASF under its Kollidon VA64™) mixed withmagnesium may be used, such as stearate and other similar excipients.Povidone, which is supplied by BASF under its Kollidon K 30™, andhydroxypropyl methylcellulose, which is supplied by Dow under itsMethocel E-15™, can also be used in certain example embodiments.

In certain example embodiments, the slowly dissolving portion of thedual release dosage form capsule, such as the slowly dissolving cap, caninclude one or more agents that do not disintegrate (or change theirstructural integrity) in the stomach and during the period that thecapsule resides in the stomach. Representative materials that keep theirintegrity in the stomach can include (a) keratin, keratin sandarac-tolu,salol (phenyl salicylate), salol beta-naphthylbenzoate and acetotannin,salol with balsam of Peru, salol with tolu, salol with gum mastic, saloland stearic acid, and salol and shellac; (b) formalized protein,formalized gelatin, and formalized cross-linked gelatin and exchangeresins; (c) myristic acid-hydrogenated castor oil-cholesterol, stearicacid-mutton tallow, stearic acid-balsam of tolu, and stearic acid-castoroil; (d) shellac, ammoniated shellac, ammoniated shellac-salol,shellac-wool fat, shellac-acetyl alcohol, shellac-stearic acid-balsam oftolu, and shellac n-butyl stearate; (e) abietic acid, methyl abictate,benzoin, balsam of tolu, sandarac, mastic with tolu, and mastic withtolu, and mastic with acetyl alcohol; (f) acrylic resins represented byanionic polymers synthesized from methacrylate acid and methacrylic acidmethyl ester, copolymeric acrylic resins of methacrylic and methacrylicacid and methacrylic acid alkyl esters, copolymers of alkacrylic acidand alkacrylic acid alkyl esters, acrylic resins such asdimethylaminoethylmethacrylate-butylmethacrylate-methylmethacrylatecopolymer of 150,000 molecular weight, methacrylic acid-methylmethacrylate 50:50 copolymer of 135,000 molecular weight, methacrylicacid-methylmethacrylate-30:70-copolymer of 135,000 mol. wt., methacrylicacid-dimethylaminoethyl-methacrylate-ethyl acrylate of 750,000 mol. wt.,methacrylic acid-methyl methacrylate-ethyl acrylate of 1,000,000 mol.wt., and ethyl acrylate-methyl methacrylate-ethyl acrylate of 550,000mol. wt; and, (g) an enteric composition including cellulose acetylphthalate, cellulose diacetyl phthalate, cellulose triacetyl phthalate,cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate,sodium cellulose acetate phthalate, cellulose ester phthalate, celluloseether phthalate, methylcellulose phthalate, cellulose ester-etherphthalate, hydroxypropyl cellulose phthalate, alkali salts of celluloseacetate phthalate, alkaline earth salts of cellulose acetate phthalate,calcium salt of cellulose acetate phthalate, ammonium salt ofhydroxypropyl methylcellulose phthalate, cellulose acetatehexahydrophthalate, hydroxypropyl methylcellulose hexahydrophthalate,polyvinyl acetate phthalate diethyl phthalate, dibutyl phthalate,dialkyl phthalate wherein the alkyl includes from 1 to 7 straight andbranched alkyl groups, aryl phthalates, and other materials known to oneor ordinary skill in the art.

As those skilled in the art will appreciate based on this disclosure, avariety of fill materials can be used with the dual release dosage formas described herein, the fill materials including various activeingredients and non-active ingredients. In certain example embodiments,the first fill material 36 positioned in the first shell body 1 caninclude the same or substantially the same active ingredient as thesecond fill material 37 positioned in the second shell body 2. Suchembodiments are particularly useful to extend the release of a givendrug. For example, the first fill material 36 can include apharmaceutical agent that can be quickly released, thereby providing aninitial dosage of the pharmaceutical when the dual release dosage formis exposed to fluids such as digestive fluids. The second fill material37, in such embodiments, can include the same pharmaceutical agent, thesecond half of the capsule being configured however to release thepharmaceutical agent after the initial dosage as described herein.Hence, the overall release of the same pharmaceutical agent is extended.For example, the overall release of the pharmaceutical agent can beextended by about 30, 40, 50, 60, 70, 80, 90, 100, 110 minutes or moreas compared to a single dosage of the pharmaceutical agent. In certainexample embodiments, the release is extended by about 2, 3, 4, 5, 6, 7,8, 9, or 10 hours.

Alternatively, in certain example embodiments the active ingredients orpharmaceutically acceptable salts thereof of the first fill material 36can be different than the active ingredients or pharmaceuticallyacceptable salts thereof of the second fill material 37. The fillmaterial positioned in the capsules, such as the first fill material 36,the second fill material 37 and any other number of fill materials, canbe any material known in the art, such as those commonly included incapsules. For example, the first fill material 36 can include ibuprofenas the active ingredient and the first cap 7 is formulated to rapidlyrelease the ibuprofen. In the same dual release dosage capsule, forexample, the second fill material 37 can include acetaminophen as theactive ingredient and the cap 8 is formulated and/or configured toslowly release the acetaminophen as described herein. Hence, ingestionof such a dosage form results in an initial release of ibuprofen that isfollowed by a later (delayed) release of acetaminophen. Such a dualrelease, for example, provides two fever reducers and pain relievers inthe same dosage form, thus dispensing with the common need to separatelyadminister ibuprofen and acetaminophen at different times.

While the above example relates to ibuprofen and acetaminophen, the fillmaterials 36, 37 can include any active ingredients or combination ofactive ingredients, including pharmaceutical agents and/ornutraceuticals. For example, if the desired effect of the capsule istargeted toward urinary tract health, an example active ingredient ofcranberry, such as cranberry extract, can be included as the activeingredient of the fill material. If the desired effect is heart health,the active ingredient can include an emulsified fatty acid, such as anemulsified omega-3 or omega-7 fatty acid. In certain exampleembodiments, the active ingredient is palmitoleic acid. In certainexample embodiments, the active ingredient is Omega-9. In certainexample embodiments, the active ingredient is hyaluronic acid. Theactive ingredient can also include any medicaments, vitamins, minerals,fruits, herbals, and/or other materials or combinations thereofunderstood by those skilled in the art to support a desired effect. Forexample, if the effect desired is mineral supplementation, exemplaryactive ingredients can be calcium, magnesium and Vitamin D. In certainexample embodiments, the active ingredient can include krill oil, salmonoil, and/or flax seed oil, such as highly purified flax seed oil. Incertain example embodiments, mixtures of active ingredients can beincluded in the fill material, such that a given dual release dosagecapsule may include 1, 2, 3, 4, 5, 6, or 7 or more active ingredients.

In addition to active ingredients, the fill materials described hereincan include a variety of other non-active components, such as non-activecomponents that are typically included in pharmaceutical and/ornutraceutical formulations. For example, the fill material can include aliquid carrier and active ingredient, the active ingredient beingsuspended within the liquid carrier. In certain example embodiments, theliquid carrier is a water-immiscible liquid, such as a vegetable and/oraromatic oil, an aromatic and aliphatic and aliphatic hydrocarbon, achlorinated hydrocarbon, an ether, an ester, high molecular weightorganic acid and/or alcohol, or lower molecular weight polyalkyleneglycol. Other embodiments can contain water-miscible liquid carriers aswell. In certain example embodiments, the active ingredients of the fillmaterial may be formulated as pharmaceutically acceptable salts.

In certain example embodiments—and distinct from the dual time releaseachieved via the structural design of the dual release dosage formcapsules described herein—the active ingredient or ingredients in one orboth fill materials 36, 37 can be formulated to modify the release rateof the active ingredient. For example, the active ingredient can beembedded in a matrix of one or more insoluble, such that the dissolvingactive ingredient must find its way out through the holes in the matrix(thus slowing the release). In certain example embodiments, the matrixcan physically swell to form a gel, thus allowing the active ingredientto exit through the gel's outer surface. In certain example embodiments,the active ingredient is coated or layered with a slow-release material.In other example embodiments, the microencapsulation can be used tomodify and further control the release of the active ingredient. Incertain example embodiments, the slow-release formulation of the activeingredient may be an extended-release dosage that includes asustained-release and/or controlled-release dosage, as known in the art.

Such slow-release formulations, which are generally known in the art,can be used in conjunction with the dual release capsules describedherein to further delay the release of active ingredient from the fillmaterials. For example, the first fill material 36 can be a rapidrelease material that, upon contact with gastric fluids, quicklyreleases the active ingredient into the environment surrounding thedosage form. The cap 8 may be formulated to slowly dissolve, therebydelaying the release of the second fill material 37 relative to thefirst fill material 36 as described herein. Yet further, the second fillmaterial 27 can include binders, excipients, matrices and/or othercomponents associated with the active ingredient that function to slowthe dissolve-time, for example, of the active ingredient of the secondfill material 37. Hence, delay in release of the active ingredient fromthe second fill material 37 can result from both the cap 8 that isformulated to slowly dissolve and secondarily the slow-releaseformulation of the active ingredient in the second fill material 37. Incertain example embodiments, the slow-release formulation of the activeingredient may be an extended-release dosage that includes asustained-release and/or controlled-release dosage, as known in the art.

As those skilled in the art will appreciate, many active ingredients arebeneficial when consumed together. For example, two or more activeingredients may act synergistically when consumed together. However, notall active ingredients or fill materials can be mixed together withinthe same dosage form, as certain active ingredients and/or fillmaterials can be incompatible with each other. For example, chemicalreactions may occur that destabilize the mixed active ingredients orthat result in gas evolution. Or, the pH needed to dissolve or suspendtwo active ingredients may be different, thus preventing the two activeingredients from being mixed within the same dosage form.

In certain example embodiments, provided is a dual dosage form capsulein which the fill materials having different pH values. For example, thefirst fill material has a pH of about 2, 3, 4, 5, or 6, whereas thesecond fill material has a pH of about 7, 8, 9, or 10. Such embodimentsare particularly useful when different pH values are required todissolve, suspend, stabilize, or otherwise mix different activeingredients. For example, the first fill material can include an oliveleaf extract, such as oleuropein, which is typically adjusted to a pH ofaround 6-7. The second fill material can include, for example, vitamin Cand/or elderberry juice at a pH of around 2-5. Such embodiments, forexample, can prevent destabilization of the oleuropein that can occur ifthe pH of the oleuropein is reduced to around 3.5 pH.

In certain example embodiments, provided is a dual dosage form capsulethat includes one or more antioxidants and a fatty acid as the fillmaterials. For example, the first fill material can include reducedglutathione (GSH) while the second fill material can include an omegafatty acid, such omega-3, 5, 6, 7, 9. As those skilled in the art willappreciate, GSH is a metal chelator that is used in detoxificationscenarios. GSH, however, is not stable when subjected to long-termstorage in solution, where metal cations are present in the solution.The thiol group on the glutathione undergoes gradual oxidation to adisulfide, a reaction that is catalyzed by the presence of molecularoxygen or of certain metal ions, such as Fe⁺³ or Cu⁺². As the reactionproceeds, there is a gradual reduction in the efficacy of the reducedglutathione solution, thus reducing its antioxidant ability. Fatty acidcompositions such as fish oil or krill oil, for example, include cationssuch as Fe⁺³ and thus cannot be mixed with GSH if the antioxidantactivity of the GSH is to be preserved. It is nevertheless beneficial toconsume such oils together with GSH because it is believed that suchoils and GSH act synergistically to improve brain health.

In certain example embodiments, beneficial ingredients that negativelyaffect fatty acids can be separated from the fatty acids with the dualdosage form capsules described herein. As those skilled in the art willappreciate, copper and iron ions, for example, are strong chemicalcatalysts in the oxidation reaction of fish oil, resulting in toxicityof the fish oil. Such metal cations can also oxidize lutein andzeaxanthin, thus reducing the efficacy of these antioxidants. CurrentAREDI and AREDII (Age-Related Eye Disease Studies I & II)recommendations, however, indicate that in combining fish oil, lutein,Zeaxanthin, Copper, Zinc and vitamin C work synergistically to supporteye health and prevent eye-related diseases such as age-related maculardegeneration. Hence, multiple refinery processes—such as bleaching,steam deodorization, etc.—are used to reduce the level of these metals.The dual dosage form capsules, however, can be configured to includecopper, zinc and/or vitamin C in the first fill material, while fishoil, lutein, and/or zeaxanthin can be included in the second fillmaterial, thus providing for the delivery of multiple, beneficialingredients.

In certain example embodiments, provided is a dual dosage form capsulethat targets different regions of the gastro-intestinal system. Forexample, the first fill material may include an active ingredient thattargets the stomach and/or small intestine, while the second fillmaterial can include an active ingredient that targets the colon. Thatis, the first capsule member 20, 20′, 20″ or shell body 1 can beconfigured as described herein so that its contents are released in thestomach and/or small intestine. The second capsule member 30, 30″, orshell body 2 can be configured so that the active ingredient is releasedin the colon, for example. In this way, one or more active ingredientscan be targeted to different regions of the gastrointestinal system.

In certain example embodiments, provided is a dual dosage form capsulethat includes two or more different probiotics. For example, the firstfill material can include a probiotic that is targeted to the stomach,whereas the second fill material can include a probiotic that istargeted to the small intestine. Example probiotics that can be usedwith any of the dual dosage form capsule embodiments described hereininclude Lactobacillus acidophilus, Lactobacillus ahamnosus,Lactobacillus helveticus, Bifidobacterium infantis, Bifidobacteriumlactis, Lactobacillus bulgaricus, Lactobacillus silivarius,Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus casei,Bifidobacterum bifidum, Saccharomyces boulardii, Streptococcusthermophilus, Bifidobacterum breve, Bacillus coagulans, Lactobacillusbrevis, Lactobacillus paracasei, Bifidobacterium longum, Lactobacillusjohnsonii, Lactobacillus fermentum, and Pediococcus acidlacti.

In certain example embodiments, the first fill material can include anantibiotic, such as amoxicillin, clarithromycin, and/or metronidazole,while the second fill material includes a probiotic. In certain exampleembodiments, the first fill material and the second fill materialinclude different antibiotics. In certain example embodiments, the firstfill material includes an antibiotic while the second fill materialincludes a proton pump inhibitor, such as omeprazole, lansoprazole,dexlansoprazole, esomeprazole, pantoprazole, rabeprazole, or ilaprazole.

In certain example embodiments, the dual dosage form capsules caninclude a probiotic in the first fill material and a prebiotic (orprebiotic rich foodstuff) in the second fill material. Such aconfiguration, for example, prevents the prebiotic from prematurelyactivating and/or affecting the probiotic before the dosage form isconsumed. Example prebiotics include dietary fibers, such aspolysaccharides and oligosaccharides, that can increase the number ofprobiotic organisms, which leads to the benefit conferred by theprobiotic. The prebiotic can include, for example, an oligosaccharide, afructo-oligosaccharide such as a soy fructo-oligosaccharide, inulin orbanana fiber, a pectin or pectic polysaccharide, a mannan, such as guargum, locust bean gum, konjac, or xanthan gum, a pentosan, beta-glucan,arabinan and galactan, such as larch arabinogalactan, and mixturesthereof. Other components that can support probiotics include, forexample, colostrum and butyric acid. In certain example embodiments, theprebiotic is PreforPro™. In certain example embodiments, the probioticis galactoooligosaccharide (GOS).

In certain example embodiments, such as softgels, heat is required touniformly distribute the probiotic with the fill material of thesoftgel. As those skilled in the art will appreciate, however, heat cankill or inactivate the probiotic. The dual dosage form capsules addressthis issue by allowing, for example, the probiotic to be present in adifferent form, such as a powder, in one shell body 1 while anotheringredient can be placed in the second shell body 2. Hence, heat is notneeded to disperse the probiotic.

In certain example embodiments, provided is a dual dosage form capsulethat reduces or prevents gas evolution. As those skilled in the art willappreciate, adding an acidic active ingredient to any carbonate solutioncan result in gas evolution. Potassium carbonate and sodium carbonate,for example, can react with Vitamin C to produce carbon dioxide. Sodiumand potassium, however, aid in the absorption of Vitamin C (andQuercitin especially in the reduction of histamine), and hence arebeneficially consumed with Vitamin C and Quercitin. Thus, provided is adual dosage form capsule that includes a mineral carbonate, such assodium or potassium carbonate, in the first fill material and an acidicactive ingredient, such as vitamin C, in the second fill material.

Manufacturing the Capsule

The systems and devices for manufacturing the capsules include at leasta capsule body filling device 100 (illustrated in FIG. 9) sized andconfigured to fill and seal the first and second capsule members 20,20′, 20″, 30, 30″ and various capsule halves described above and acapsule forming device 200 (illustrated in FIG. 10) sized and configuredto couple the capsule members with the band 3, or shell bodies 1, 2, orcapsule members with the first capsule members 20′, 20″, 30″ to form thecapsules. The capsule body filling device 100 and the capsule formingdevice 200 can be formed from rigid materials, such as metal, wood,ceramics, polymeric materials and the like.

Referring to FIG. 9, the capsule body filling device 100 includes asubstantially planar rotating disc 102 sized and configured to hold andposition a shell body 1, 2. For example, a plurality of pockets 106defined in an upper surface 108 of the rotating disc are positionedadjacent to a perimeter 110 of the rotating disc. Each pocket 106 issized and configured to hold at least a portion of a shell body 1, 2therein. In one example, at least a portion of a pocket wall 112 can bearcuate in shape to correspond to the arcuate closed end 12, 22 of theshell body (see pocket wall 206 in FIG. 11). For example, at least aportion of the pocket wall can be semi-spherical so that the closed endof the shell body can be positioned in the pocket 106, with the open end11, 21 of the shell body facing away from the rotating disc 102. Therotating disc 102 can have a rotational axis AR extending through thecenter of the disc. In certain example embodiments, the rotational axisof the rotating disc can be substantially normal to the upper surface108 of the rotating disc (i.e. out of the page in FIG. 9).

The capsule body filling device 100 further includes a plurality ofdispensing devices 114. For example, the plurality of dispensing devicescan include at least one of a shell body dispenser 116, at least onepharmaceutical dispenser 118 and a cap or band dispenser 120. In certainexample embodiments, the plurality of dispensing devices 114 can bepositioned above the rotating disc 102 so that as the disc rotates, thepockets 106 can move adjacent to a portion of the desired dispensingdevice.

In certain example embodiments, the shell body dispenser 116 can besized and configured to position a shell body 1, 2 in a pocket of theplurality of pockets 106 of the rotating disc 102. For example, theshell body dispenser includes a shell body hopper 122 and a shell bodytrack 124. In one example, the shell body hopper can be a containersized and configured to hold a plurality of shell bodies 1, 2. That is,the shell body hopper 122 can have a storage chamber 126 for a pluralityof shell bodies. In another example, the shell body track 124 can beconfigured to convey shell bodies 1, 2 from the shell body hopper to therotating disc 102. For example, the shell body track can include a shellbody tube 128 having a first end 130 coupled to the shell body hopper122 and a second end 132 positioned adjacent a pocket 106 of therotating disc. In use, the shell bodies in the shell body hopper can begravity fed through an inner lumen of the tube and to a pocket 106 inthe rotating disc 102. Optionally, the shell bodies 1, 2 can bepneumatically urged through the inner lumen of the shell body tube 128.For example, positive air pressure at the first end of the tube and/ornegative air pressure (a vacuum) at the second end of the tube 128 canurge the shell bodies 1, 2 through the inner lumen of the tube and to apocket in the rotating disc 102.

In certain example embodiments, the shell body track 124 can include ashell body conveyor, such as an endless conveyor belt and the likehaving a first end adjacent the shell body hopper 122 and a second endadjacent a pocket 106 in the rotating disc 102. In this example, theshell body conveyor can be sized and configured to carry shell bodies 1,2 from the shell body hopper to the rotating disc.

In still another example embodiment, the shell body track 124 and/or therotating disc 102 can be configured so that the shell bodies 1, 2 arepositioned in a pocket 106 of the rotating disc with the closed end 12,22 of the shell body contacting the upper surface 108 of the rotatingdisc 102 and with the open end 11, 21 of the shell body 1, 2 facing awayfrom the rotating disc so that the distal edge 17, 27 of the firstsidewall 13 or second sidewall 23 is spaced from the upper surface ofthe rotating disc a predetermined distance.

The pharmaceutical dispenser 118 can be sized and configured to insert afill material 36, 37 into the respective first and second chambers 5, 6of a shell body 1, 2 positioned in a pocket of the plurality of pockets106 of the rotating disc 102. In one example embodiment, thepharmaceutical dispenser can include a pharmaceutical hopper 136 and apharmaceutical track 138. In another example embodiment, thepharmaceutical hopper can be a container sized and configured to holdthe fill material 36, 37, such as a pharmaceutical and the like therein.That is, the pharmaceutical hopper 136 can have a storage chamber 140configured to hold a liquid fill material, a granular fill material, ora powder fill material as desired. The pharmaceutical track 138 can beconfigured to convey the fill material from the pharmaceutical hopper tothe rotating disc 102. For example, the pharmaceutical track can includea pharmaceutical tube 142 having a first end 144 coupled to thepharmaceutical hopper 136 and a second end 146 positioned adjacent to ashell body 1, 2 in pocket 106 of the rotating disc. In use, the fillmaterial 36, 37 in the pharmaceutical hopper can be gravity fed throughan inner lumen of the pharmaceutical tube and through the open end 11,21 in a shell body into the first and second chamber 5, 6 of a shellbody 1, 2 in a pocket 106 in the rotating disc 102. Optionally, the fillmaterial can be pneumatically urged through the inner lumen of thepharmaceutical tube 142. For example, positive air pressure at the firstend of the tube and/or negative air pressure (a vacuum) at the secondend of the tube 142 can urge the fill material through the inner lumenof the tube and to shell bodies 1, 2 in the rotating disc 102.

In certain example embodiments, the pharmaceutical track 138 can includea pharmaceutical conveyor, such as an endless conveyor belt and the likehaving a first end adjacent the pharmaceutical hopper 136 and a secondend adjacent to a shell body 1, 2 in a pocket 106 of the rotating disc102. In such examples, the pharmaceutical conveyor can be sized andconfigured to carry a fill material from the pharmaceutical hopper tothe rotating disc 102.

Optionally, the pharmaceutical dispenser 118 can include a plurality ofpharmaceutical dispensers. In certain example embodiments, a firstpharmaceutical dispenser can be configured to deliver the first fillmaterial 36 to the shell bodies 1, 2 in the rotating disc 102 and asecond pharmaceutical dispenser can be configured to deliver a secondfill material 37 to the shell bodies in the rotating disc, wherein thefirst fill material is the same or different than the second fillmaterial. For example, the first pharmaceutical dispenser can beconfigured to deliver a liquid fill material to the shell bodies 1, 2and the second pharmaceutical dispenser can be configured to deliver apowder fill material. Of course, it is contemplated that the pluralityof pharmaceutical dispensers can include 3, 4, 5, 6, 7, 8, 9, 10 or morethan 10 pharmaceutical dispensers, each pharmaceutical dispenserconfigured to deliver a fill material to the shell bodies in therotating disc 102.

In certain example embodiments, the cap or band dispenser 120 can besized and configured to position a cap such as the first cap 7 and thesecond cap 8 onto a shell body 1, 2 positioned in a pocket 106 of therotating disc 102 or a band 43, 43′, 71 or 72 onto a shell body 1, 2.For example, the cap or band dispenser includes a hopper 148 and a track150. In one example embodiment, the hopper 148 can be a container sizedand configured to hold a plurality of caps or bands. That is, the hopper148 can have a storage chamber 152 for a plurality of caps or pluralityof bands. In a further example embodiment, the track 150 can beconfigured to convey the caps or bands from the hopper to the rotatingdisc 102. For example, the track 150 can include a tube 154 having afirst end 156 coupled to the hopper 148 and a second end 158 positionedadjacent pocket 106 of the rotating disc. In another example embodiment,the hopper 148 and/or the track 150 can be sized and configured to holda plurality of caps or bands in a stacked position as illustrated inFIG. 9. In use, the caps or bands in the hopper 148 can be gravity fedthrough an inner lumen of the tube 154 and to a shell body 1, 2 in therotating disc 102. Optionally, the caps or bands can be pneumaticallyurged through the inner lumen of the tube. For example, positive airpressure at the first end 156 of the tube and/or negative air pressure(a vacuum) at the second end 158 of the tube 154 can urge the caps orbands through the inner lumen of the tube and to a shell body in therotating disc 102.

In certain example embodiments, the track 150 can include a conveyor,such as an endless conveyor belt and the like having a first endadjacent the hopper 148 and a second end adjacent to shell body 1 or 2in the rotating disc 102. In such examples, the conveyor can be sizedand configured to carry caps or bands from the hopper to the rotatingdisc.

The capsule body filling device 100 further includes a sealing device160 configured to seal the cap 7, 8 or band 43, 43′, 71 or 72 to a shellbody 1 or 2 and form the respective capsule member 20, 20′, 20″, 30,30″. In one example embodiment, the sealing device includes at least onelaser 162. In such examples, the laser can be a focused laser directedtoward at least a portion of the cap and/or the shell body so that thelaser 162 can heat seal the cap 7, 8 or band 43, 43′, 71 or 72 to ashell body 1 or 2, thereby forming a capsule member. In another exampleembodiment, the laser can heat seal the cap or band to the shell body ata temperature of between about 70° F. and 120° F. Optionally, the laser162 can heat seal the cap or band to the shell body 1, 2 at atemperature of between about 80° F. and 110° F. In a further exampleembodiment, the laser can include a plurality of lasers. Thus, asdescribed more fully below, when the rotating disc 102 rotates with thecaps and shell bodies positioned therein, each laser 162 of theplurality of lasers can be directed toward a cap or band and/or shellbody 1, 2 at a predetermined rotational position.

In certain example embodiments, the sealing device 160 includes at leastone heater 164. In this example embodiment, the heater can be a focusedheater directed toward the cap 7, 8 or band 43, 43′, 71 or 72 and/or theshell body 1, 2 so that the heater 164 can heat seal the cap or band tothe shell body and form a capsule member. In certain exampleembodiments, the heater can heat seal the cap or band to the shell body1, 2 at a temperature of between about 70° F. and 120° F. Optionally,the heater 164 can heat seal the cap or band to the shell body at atemperature of between about 80° F. and 110° F. In a further exampleembodiment, the heater can include a plurality of heaters. Thus, asdescribed more fully below, when the rotating disc 102 rotates with thecaps or band and shell bodies 1, 2 positioned therein, each heater 164of the plurality of heater can be directed toward a cap or band and/orshell body at a predetermined rotational position.

The capsule body filling device 100 further includes a capsule membercooling device 166 configured to cool the filled, sealed capsule members20, 20′, 20″, 30, 30″. For example, the capsule member cooling devicecan include a chiller configured to direct chilled air or other chilledfluid toward the capsule members positioned in the rotating disc 102. Incertain example embodiments, the cooling device 166 can be sized andconfigured so that at least a portion of the rotating disc 102 rotatesbetween a portion of the cooling device. For example, the cooling device166 can be a “C” shaped cooling device sized and configured so that atleast a portion of the rotating disc rotates between a portion of thecooling device. In certain example embodiments, the cooling device 166can cool the capsule member at a temperature of between about 35° F. and65° F. Optionally, the cooling device can cool the capsule member at atemperature of between about 45° F. and 55° F.

Referring now to FIG. 10, the capsule forming device 200 can be sizedand configured to couple (i) a first capsule member 20 and a secondcapsule member 30 with the band 3 to form the capsule 10, (ii) an emptyshell body 1, 2 that is filled with a fill material and a capsule member20′ having a band 43, 43′ already sealingly connected thereto, (iii) afirst capsule member 20 and a capsule member 20′ having a band 43, 43′already sealingly connected thereto, or (iv) a first capsule member 20″and a second capsule member 30″. At least portions of the capsuleforming device can be formed from rigid materials, such as metal, wood,ceramics, polymeric materials and the like.

Sample configurations of rotating plates, filling mechanisms, andpositive or negative pressure systems are described in U.S. Pat. Nos.4,964,262 and 3,070,932. As representatively illustrated in FIG. 10, thecapsule forming device 200 includes a pair of superimposed rotatingplates, lower plate 202 and upper plate 203, wherein each rotating platehas a plurality of voids 206 sized and configured to hold a shell body 1or 2 and/or capsule member 20, 20′, 20″, 30, or 30″ therein. The lowerplate 202 has an upper plate surface 208 and the upper plate 203 has alower plate surface 210 facing one another. A plurality of voids 206 aredefined in the upper surface 208 of the lower plate 202 and the lowerplate surface 210 of the upper plate 203. In such examples, theplurality of voids 206 are positioned adjacent to a perimeter 214 ofeach rotating plate but are not limited thereto.

In the upper plate 203, the voids 206, as best seen in FIG. 11, passthrough the plate as a bore from the lower plate surface 210 to theupper plate surface 211 and are dimensioned to receive a capsule membertherethrough that has a cap or band sealingly connected thereto. Assuch, the capsule member can be introduced into the upper plate 203through the upper plate surface 211 with the cap or band oriented towardto lower plate 202 (i.e., the cap or band enters the void 206 first).The upper plate 203 includes a plurality of pressure flow pathways 213to each void 206 to apply negative pressure from a pressure source P tohold each capsule member in a predetermined position with the cap and/orband extending beyond the lower plate surface 210 toward the lower plate202. In any embodiment where a shell body is to receive a cap or acapsule member is to receive a band, the shell body or capsule membershould protrude beyond the lower plate surface 210 of the upper plate203 or the upper plate surface 208 of the lower plate 202 by a distancein a range of 0.015 inch (0.38 mm) to 0.030 inch (0.76 mm).

As shown for the lower plate 202 in FIG. 11, at least a portion of avoid wall 212 can be arcuate in shape to correspond to the closed end12, 22 of the shell body 1, 2 of the capsule member. For example, atleast a portion of the void wall 212 can be semi-spherical so that theclosed end of the capsule member can be positioned in void 206, with thecap 7, 8 or band of the capsule member or an open end of the shell body1, 2 facing away from the lower plate 202 in which it is positioned. Instill another example embodiment, a vacuum can be applied to each voidin the upper and/or lower plates 202, 203 to securely hold at least aportion of the capsule member within the void. Alternatively, gravityand/or a friction fit between the wall 212 of the void 206 and thecapsule members or shell body can securely hold the same in the lowerplate 202.

The lower plate 202 has a rotational axis A_(P1) extending through thecenter thereof that is substantially normal to the upper plate surface208 of the first plate 204, and the upper plate 203 has a rotationalaxis A_(P2) extending through the center thereof that is substantiallynormal to the lower plate surface 210. The rotational axis A_(P1) of thelower plate 202 and the rotational axis A_(P2) of the upper plate 203are co-axially aligned. In a first position, the lower plate 202 can bespaced from the upper plate 203 a predetermined distance that is thesame distance around the perimeter 214 of the plates.

Referring to FIG. 12, the actuator 280 pivots the upper plate 203 or thelower plate 202 relative to the other (the upper plate 203 in FIG. 12)axially to move one plate position 218 toward the other plate and anopposing plate position 220 away from the other plate. The actuator 280is also shown in FIG. 10 for further reference. With one of the plates202 or 203 pivoted as such, the first plate position 218 has the platesspaced a distance apart D₁ and the second plate position 218 spacedapart a distance D₂, where D₂ is greater than D₁. The pivoting of one ofthe plates 202 or 203 can provide a downward or an upward force,respectively to push the capsule member(s) into or onto the band for asnap-fit, click-fit, interference fit, friction fit, or telescoping fit.Alternately or additionally, positive pressure can be applied using airflow to push the capsule member(s) toward the band. Also, the actuator280 has the ability to lift the upper plate 203 or lower the lower plate202 relative to the other plate such that assembled capsules are removedfrom the upper plate 203 and can rotate thereafter in just the lowerplate 202 to subsequent sealing and cooling stations.

Referring to FIG. 13, in another embodiment, the rotational axis A_(P1)of the lower plate 202 can be at an acute angle θ relative to therotational axis A_(P2) of the upper plate 203 such that the uppersurface 208 of the first plate is at an acute angle relative to thelower surface 210 of the second plate. In this example embodiment, thelower plate 202 can be spaced from the upper plate 203 a predetermineddistance that varies around the perimeter 214 of the plates. Forexample, at a first plate position 218, the upper surface 208 of thelower plate 202 can be spaced a first predetermined distance from thelower surface 210 of the upper plate 203 and at a second plate position220, the upper surface 208 of the lower plate 202 can be spaced a secondpredetermined distance from the lower surface 210 of the upper plate 203that is less than the first plate position.

As can be appreciated, in one example embodiment, the rotational axisA_(P1) of the lower plate 202 and/or the rotational axis A_(P2) of theupper plate 203 can be substantially vertical as illustrated in FIGS. 11and 12, such that at least one of the plates 202 rotates in asubstantially horizontal plane. In another example embodiment, asillustrated in FIG. 13, the rotational axis A_(P1) of the lower plate202 and/or the rotational axis A_(P2) of the upper plate 203 can bebetween vertical and horizontal such that at least one of the plates 202rotates in a plane that is between horizontal and vertical. In stillanother example embodiment, the rotational axis A_(P1) of the lowerplate 202 and/or the rotational axis A_(P2) of the upper plate 203 canbe substantially horizontal (not illustrated), such that at least one ofthe plates 202 rotates in a substantially vertical plane.

In certain plate positions, each void 206 in the upper surface 208 ofthe lower plate 202 can be aligned with a void in the lower surface 210of the upper plate 203. A longitudinal axis A_(V1) of each void in thelower plate 202 can be substantially coaxially aligned with alongitudinal axis A_(V2) of each void in the upper plate 203 for atleast one plate position or for a portion of a revolution of the upperand lower plates 202, 203. Thus, in use as described more fully below, afirst capsule member positioned in a void 206 in the upper surface 208of the lower plate 202 can be aligned with a second capsule memberpositioned in a void in the lower surface 210 of the upper plate 203.

For example, if the rotational axis A_(P1) of the lower plate 202 is atan acute angle relative to the rotational axis A_(P2) of the upper plate203, the longitudinal axis A_(V1) of a void 206 in the first plate canbe substantially coaxially aligned with the longitudinal axis A_(V2) ofa void in the second place for at least a portion of the revolution ofthe plates. In another example, if the rotational axis A_(P1) of thelower plate 202 is at an acute angle relative to the rotational axisA_(P2) of the upper plate 203, the longitudinal axis A_(V1) of a void206 in the first plate can be substantially coaxially aligned with thelongitudinal axis A_(V2) of a void in the second plate, with the firstand second plates at any position about and between the first plateposition 218 and the second plate position 220.

The capsule forming device 200 further includes a plurality ofdistribution devices 222. For example, the plurality of distributiondevices can include at least one first capsule member or shell bodydistributor 224, a second capsule member distributor 226, and a band orfill distributor 228. In one example embodiment, the plurality ofdistribution devices 222 can be positioned adjacent the plurality ofrotating plates 202, 203 so that as the plates rotate, the voids 206 inthe plates can move adjacent to the desired distribution device.

The first capsule member distributor 224 can be sized and configured toposition the first capsule member 20 or 20″ or a shell body 1, 2 in avoid 206 of the plurality of voids of the first rotating plate 204. Forexample, the first capsule member distributor includes a first hopper230 and a first track 232. In certain example embodiments, the firsthopper can be a container sized and configured to hold a plurality offirst capsule members 20 or 20″ or a shell body 1, 2. That is, the firsthopper 230 can have a storage chamber 234 for a plurality of firstcapsule members or shell bodies. In another example embodiment, thefirst track 232 can be configured to convey first capsule members 20 or20″ or a shell body 1, 2 from the first hopper to the lower plate 202.For example, the first track 232 can include a first tube 236 having afirst end 238 coupled to the first capsule member hopper 230 and asecond end 240 positioned adjacent void(s) 206 of the first rotatingplate. In use, the first capsule members 20 or 20″ or a shell body 1, 2in the first hopper can be gravity fed through an inner lumen of thefirst tube and to void(s) 206 in the upper surface 208 of the lowerplate 202. Optionally, the first capsule member 20 or 20″ or a shellbody 1, 2 can be pneumatically urged through the inner lumen of thefirst tube 236. For example, positive air pressure at the first end ofthe tube and/or negative air pressure (a vacuum) at the second end ofthe first tube 236 can urge the first capsule member 20 or 20″ or ashell body 1, 2 through the inner lumen of the tube and to a void in thelower plate 202.

In another example embodiment, the first track 232 can include a firstconveyor, such as an endless conveyor belt and the like having a firstend adjacent the first hopper 230 and a second end adjacent a void 206in the lower plate 202. In this example embodiment, the first conveyorcan be sized and configured to carry first capsule members 20, 20″ or ashell body 1, 2 from the first hopper to the lower plate 202.

The second capsule member distributor 226 can be sized and configured toposition the second capsule member 20′, 30, or 30″ in void(s) 206 of theupper plate 203. For example, the second capsule member distributor 226includes a second hopper 242 and a second track 244. In one exampleembodiment, the second hopper 242 can be a container sized andconfigured to hold a plurality of second capsule members 20′, 30, or30″. That is, the second hopper 242 can have a storage chamber 246 for aplurality of second capsule members 20′, 30, or 30″. In another exampleembodiment, the second track 244 can be configured to convey secondcapsule members 20′, 30, or 30″ from the second hopper to the upperplate 203. For example, the second track can include a second tube 248having a first end 250 coupled to the second hopper 242 and a second end252 positioned adjacent a void 206 of the upper plate 203. In use, thesecond capsule members 20′, 30, or 30″ in the second hopper can begravity fed through an inner lumen of the second tube and to void(s) 206in the lower surface 210 of the upper plate 203. Optionally, the secondcapsule member 20′, 30, or 30″ can be pneumatically urged through theinner lumen of the second tube 248. For example, positive air pressureat the first end of the tube and/or negative air pressure (a vacuum) atthe second end of the tube 248 can urge the second capsule member 20′,30, or 30″ through the inner lumen of the tube and to void(s) 206 in theupper plate 203.

In another example embodiment, the second track 244 can include a secondcapsule member conveyor, such as an endless conveyor belt and the likehaving a first end adjacent the second hopper 242 and a second endadjacent a void 206 in the upper plate 203. In this example embodiment,the second conveyor can be sized and configured to carry second capsulemembers 20′, 30, or 30″ from the second hopper to the upper plate 203.

A third distributor 222 may be present to distribute bands 2, a fillliquid or fill powder, or may be empty. When capsule members beingassembled are the first and second capsule members 20 and 30, the thirddistributor 222 is a band distributor 228 which is sized and configuredto position the band 3 around one of the first and second capsulemembers 20, 30, whichever is in the lower plate 202. For example, theband distributor 228 includes a third hopper 254 and a third track 256.In certain example embodiments, the third hopper 254 can be a containersized and configured to hold a plurality of bands 3. That is, the thirdhopper 254 can have a storage chamber 258 for a plurality of bands. Inanother example embodiment, the third track 256 can be configured toconvey bands 3 from the third hopper to the first and second capsulemembers 20, 30. For example, the third track can include a band tube 260having a first end 262 coupled to the third hopper 254 and a second end264 positioned adjacent a first capsule member 20 in the lower plate 202and a second capsule member 30 in the upper plate 203. In use, the bands3 in the third hopper can be gravity fed through an inner lumen of theband tube 260 and to a first and second capsule members in the lowerplate 202 and upper plate 203. Optionally, the bands 3 can bepneumatically urged through the inner lumen of the band tube 260. Forexample, positive air pressure at the first end of the tube and/ornegative air pressure (a vacuum) at the second end of the tube 260 canurge the bands 3 through the inner lumen of the tube and to a first andsecond capsule members in the lower plate 202 and upper plate 203.

In another example embodiment, the third track 256 can include a bandconveyor, such as an endless conveyor belt and the like having a firstend adjacent the band 254 and a second end adjacent a first capsulemember 20 in the lower plate 202 and a second capsule member 30 in theupper plate 203. In this example embodiment, the band conveyor can besized and configured to convey bands 3 from the third hopper 254 to oneof first and second capsule member 20, 30, whichever is in the lowerplate 202.

The capsule forming device 200 further includes a capsule sealing device266 configured to seal the band 3 to the first and second capsulemembers and form the capsule. The capsule sealing device 266 may be atthe station where the two halves of the capsule are mated or at astation subsequent to the station where the two halves of the capsuleare mated as illustrated in FIG. 10 but does not need to be at bothstations. In certain example embodiments, the capsule sealing device 266includes at least one capsule sealing laser 268. In this exampleembodiment, the capsule sealing laser can be a focused laser directedtoward the band and/or the capsule members so that the capsule sealinglaser 268 can heat seal the band or band portions to the capsule membersand/or the band portions to one another thereby forming a capsule. Inanother example embodiment, the capsule sealing laser can heat seal theband or band portions to the capsule members at a temperature of betweenabout 70° F. and 120° F. Optionally, the capsule sealing laser 268 canheat seal the band or band portions to the capsule members at atemperature of between about 80° F. and 110° F. In a further exampleembodiment, the at least one capsule sealing laser can include aplurality of capsule sealing lasers. Thus, as described more fullybelow, when the lower plate 202 rotate with the band and the capsulemembers positioned therein, each capsule sealing laser 268 of theplurality of lasers can be directed toward the band and/or capsulemember at a predetermined rotational position.

In certain example embodiments, the capsule sealing device 266 includesat least one capsule sealing heater 270. In this example embodiment, theat least one capsule sealing heater can be a focused heater directedtoward the band and/or the capsule members so that the capsule sealingheater 270 can heat seal the band to the capsule members or bandportions to one another to form a capsule. In another exampleembodiment, the capsule sealing heater can heat seal the band to thecapsule members or band portions at a temperature of between about 70°F. and 120° F. Optionally, the capsule sealing heater 270 can heat sealthe band to the capsule members or band portions at a temperature ofbetween about 80° F. and 110° F. In a further example embodiment, the atleast one capsule sealing heater includes a plurality of capsule sealingheaters. Thus, as described more fully below, when the lower plate 202rotates with the band and the capsule members positioned therein, eachcapsule sealing heater of the plurality of capsule sealing heater can bedirected toward a band and/or capsule member at a predeterminedrotational position.

The capsule forming device 200 further includes a capsule cooling device272 configured to cool the assembled, sealed capsule. For example, thecapsule cooling device can include a capsule chiller 274 configured todirect chilled air or other chilled fluid toward the capsule(s)positioned in at least the lower plate 202. In certain exampleembodiments, the capsule cooling device 272 can be sized and configuredso that at least a portion of the capsule rotates between a portion ofthe capsule cooling device. For example, the capsule cooling device 272can be a “C” shaped capsule cooling device sized and configured so thatat least a portion of at least the lower plate rotate between a portionof the capsule cooling device. In certain example embodiments, thecapsule cooling device can cool the capsule(s) at a temperature ofbetween about 35° F. and 65° F. Optionally, the capsule cooling device272 can cool the capsule(s) at a temperature of between about 45° F. and55° F.

Referring back to FIG. 9, to form the first capsule member 20 of thedual release dosage form capsule 10, the first shell body 1 can beprovided to and loaded into the shell body hopper 122, the first fillmaterial 36 can be provided to and loaded into the at least onepharmaceutical hopper 136 and the first cap 7 can be provided to andloaded into the cap hopper 148. The first shell body can be urged downthe shell body track 124 from the shell body hopper 122 to a pocket 106of the rotating disc 102 with the first open end 11 of the first shellbody facing away from the rotating disc. For example, the first shellbody can be urged over the shell body track by gravity, pneumatically ormechanically. The rotating disc 102 can then rotate so that the open end11 of the first shell body 1 is adjacent to a portion of thepharmaceutical track 138.

The first fill material 36 can be urged down the pharmaceutical track138 from the pharmaceutical hopper 136, through the open end 11 of thefirst shell body 1 and into the first chamber 5 of the first shell body.For example, the first fill material can be urged over thepharmaceutical track by gravity, pneumatically or mechanically and intothe first chamber of the first shell body 1. The rotating disc 102 canthen rotate so that the open end 11 of the first shell body 1 isadjacent to a portion of the cap track 150.

The first cap 7 can be urged down the cap track 138 from the cap hopper148 and positioned over the open end 11 of the first shell body 1. Forexample, a portion of the first cover 14 and/or the first lip of thefirst cap 7 can engage a distal edge 17 of the first sidewall 13 of thefirst shell body 1 to enclose the first fill material 36 in the firstchamber 5. That is, at least a portion of the first cap can be incontact with the first shell body to enclose the first fill materialinside the first chamber. In certain example embodiments, the first cap7 can be urged over the cap track by gravity, pneumatically ormechanically. The rotating disc 102 can then rotate so that the firstshell body 1, the first fill material 36 and the first cap 7 arepositioned adjacent to and/or aligned with the sealing device 160.

In certain example embodiments, if the sealing device 160 includes atleast one laser 162, the rotating disc 102 can rotate until the firstshell body 1 and/or the first cap 7 are aligned with the laser so thelaser can seal the first cap to the first shell body, forming the firstcapsule member 20. In another example embodiment, if the sealing deviceincludes at least one heater 164, the disc can rotate until the firstshell body 1 and/or the first cap 7 are positioned to receive heat fromthe heater 164 so the heat can seal the first cap to the first shellbody, forming the first capsule member 20. The rotating disc 102 canthen rotate so that the first capsule member 20 is positioned adjacentto and/or aligned with the capsule member cooling device 166.

In certain example embodiments, if the capsule member cooling device 166includes a chiller, the rotating disc 102 can rotate until the firstcapsule member is positioned to be chilled with fluid or air from thechiller to cool the first member 20 to the desired temperature. Uponreaching the desired temperature, the first member can be dischargedfrom the rotating disc 102 by gravity, pneumatically or mechanically.

As can be appreciated, a plurality of first shell bodies 1, first fillmaterials 36 and first caps 7 can be provided to the respective hoppers,so that the capsule body filling device can produce a plurality of firstcapsule members 20 quickly and inexpensively compared to manual methodsof forming the first capsule member.

To form the second capsule member 30 of the dual release dosage formcapsule 10, the process above is repeated. The second shell body 2 canbe provided to and loaded into the shell body hopper 122, the secondfill material 37 can be provided to and loaded into the at least onepharmaceutical hopper 136 and the second cap 8 can be provided to andloaded into the cap hopper 148. The second shell body can be urged fromthe shell body hopper 122 down the shell body track 124 to a pocket 106of the rotating disc 102 with the open end 21 of the second shell bodyfacing away from the rotating disc. For example, the second shell body 2can be urged over the shell body track by gravity, pneumatically ormechanically. The rotating disc 102 can then rotate so that the open end21 of the second shell body is adjacent to a portion of thepharmaceutical track 138.

The second fill material 37 can be urged down the pharmaceutical track138, from the pharmaceutical hopper 136, through the open end 21 of thesecond shell body 2 and into the second chamber 6 of the second shellbody. For example, the second fill material can be urged over thepharmaceutical track by gravity, pneumatically or mechanically. Therotating disc 102 can then rotate so that the open end 21 of the secondshell body 21 is adjacent to a portion of the cap track 150.

The second cap 8 can be urged down the cap track 138 from the cap hopper148 and positioned over the open end 21 of the second shell body 2. Forexample, a portion of the second cover 24 and/or the second lip 25 ofthe second cap 8 can engage a distal edge 27 of the second sidewall 23of the second shell body 2 to enclose the second fill material 37 in thesecond chamber 6. That is, at least a portion of the second cap can bein contact with the second shell body to enclose the second fillmaterial inside the second chamber. In certain example embodiments, thesecond cap 8 can be urged over the cap track by gravity, pneumaticallyor mechanically. The rotating disc 102 can then rotate so that thesecond shell body 2, the second fill material 37 and the second cap 8are positioned adjacent and/or aligned with the sealing device 160.

In certain example embodiments, if the sealing device 160 includes atleast one laser 162, the rotating disc 102 can rotate until the secondshell body 2 and/or the second cap 8 are aligned with the laser so thelaser can seal the second cap to the second shell body, forming thesecond capsule member 30. In another example embodiment, if the sealingdevice includes at least one heater 164, the disc can rotate until thesecond shell body 2 and/or the second cap 8 are positioned to receiveheat from the heater 164 so the heat can seal the second cap to thesecond shell body, forming the second capsule member 30. The rotatingdisc 102 can then rotate so that the second capsule member 30 ispositioned adjacent and/or aligned with the capsule member coolingdevice 166.

In certain example embodiments, if the capsule member cooling device 166includes a chiller, the rotating disc 102 can rotate until the secondcapsule member 30 is positioned to be chilled with fluid or air, fromthe chiller to cool the second capsule member to the desiredtemperature. Upon reaching the desired temperature, the second capsulemember 30 can be discharged from the rotating disc 102 by gravity,pneumatically or mechanically.

As can be appreciated, a plurality of second shell bodies 2, second fillmaterials 37 and second caps 8 can be provided to the respective hoppersso that the capsule body filling device 100 can produce a plurality ofsecond capsule members 30 quickly and inexpensively compared to manualmethods of forming the second capsule member.

Still referring to FIG. 9, the process described above for the firstcapsule member 20 or the second capsule member 30 is repeatable to formone of the other capsule members disclosed herein by introducing a band43, 43′, 71 or 72 at the cap or band dispenser 120 to form capsulemembers 20′, 20″, or 30″.

Referring to FIG. 10, to illustrate the formation of the dual releasedosage form capsule 10 of FIG. 2, the capsule forming device 200 couplesthe first capsule member 20 to the second capsule member 30 with theband 3. The first capsule member 20 is provided to and loaded into thefirst hopper 230, the second capsule member 30 is provided to and loadedinto the second hopper 242 and the band 3 is provided to and loaded intothe third hopper 254. The first capsule member 20 is urged down thefirst track 232 from the first capsule member hopper 230 to a void 206of the lower plate 202 with the first cap 7 of the first capsule memberfacing away from the first rotating plate. The first capsule member 20can be urged over the first track by gravity, pneumatically ormechanically.

The second capsule member 30 can be urged down the second track 232 fromthe second hopper 242 to a void 206 of the upper plate 203 with thesecond cap 8 of the second capsule member facing away from the upperplate. The second capsule member 30 can be urged over the second trackby gravity, pneumatically or mechanically.

The band 3 is urged down the third track 256 from the third hopper 254to the first and second capsule members 20, 30 positioned in therespective upper and lower plates 202, 203. The band 3 can be urged overthe band track by gravity, pneumatically or mechanically. In certainexample embodiments, a portion of the first capsule member 20 can beinserted through the first entry port 34 of the band 3 and into thepassage 33 of the band, and a portion of the second capsule member 30can be inserted through the second entry port 35 and into the passage ofthe band 3. In the passage, the first capsule member can be spaced fromthe second capsule member a predetermined distance to form the thirdchamber 4.

The lower plate 202 and the upper plate 203 can rotate simultaneously(i.e. at the same velocity and at the same time) to move the firstcapsule member 20, the second capsule member 30 and the band 3 to aposition adjacent and/or aligned with the capsule sealing device 266 orthe plates 202, 203 can separate using the actuator 280 such that justthe lower plate 202 retains the capsule and rotates to the capsulesealing device 266. The capsule sealing device can direct heat towardsthe band 3 and/or the capsule members 20, 30 to seal the band to thefirst and second capsule members 20, 30 and form the capsule 10. Forexample, if the capsule sealing device 266 includes at least one capsulelaser 268, the upper and lower plates 202, 203 can rotate until the band3 and/or the capsule members 20, 30 are aligned with the capsule laserso the capsule laser can seal the band to the first and second capsulemembers 20, 30, forming the capsule 10. In another example embodiment,if the capsule sealing device includes at least one capsule heater 270,the upper and lower plates 202, 203 can rotate until the band 3 and/orthe capsule members 20, 30 are positioned to receive heat from thecapsule heater so the heat can seal the band 3 to the first and secondcapsule members 20, 3, forming the capsule 10. The upper and lowerplates 202, 203 can then rotate so that the capsule is positionedadjacent and/or aligned with the capsule cooling device 272.

In certain example embodiments, if the capsule cooling device 272 is acapsule chiller, the upper and lower plates 202, 203 can rotate untilthe capsule 10 is positioned to be chilled with fluid or air from thecapsule chiller to cool the capsule to the desired temperature. Uponreaching the desired temperature, the capsule 10 can be discharged fromthe upper and lower plates 202, 203 by gravity, pneumatically ormechanically.

As can be appreciated, a plurality of first capsule members 20, secondcapsule members 30 and bands 3 can be provided to the respective hoppersso that the capsule forming device 200 can produce a plurality ofcapsules quickly and inexpensively compared to manual methods of formingthe capsule 10.

The above-detailed description of embodiments of the disclosure is notintended to be exhaustive or to limit the teachings to the precise formdisclosed above. While specific embodiments of and examples for thedisclosure are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thedisclosure, as those skilled in the art will recognize and understand.For example, while processes can be presented in a given order,alternative embodiments can perform routines having steps in a differentorder, with some steps being deleted, moved, added, subdivided,combined, and/or modified to provide alternative or sub-combinations.Each of these processes can be implemented in a variety of differentways, as those skilled in the art will appreciate. Also, while processesare at times shown as being performed in series, these processes caninstead be performed in parallel, or can be performed, at differenttimes. Further, any specific numbers noted herein are onlyexamples—alternative implementations can employ differing values orranges.

The teachings of the disclosure provided herein can be applied to othersystems, not necessarily the system described above. The elements andacts of the various embodiments described above can be combined toprovide further embodiments. Any patents noted above that areincorporated herein by reference, for example, can be modified, asnecessary, to provide yet further embodiments of the disclosure providedherein. Further, while the above description describes certainembodiments, the teachings can be practiced in many ways that will beappreciated by those of skill in the art no matter how detailed theabove appears in text. Details of the capsule members, capsules, andrelated processes and products can vary considerably in theirimplementation details, while still being encompassed by the subjectmatter disclosed herein. Hence, although example embodiments of theinvention have been shown and described, it is to be understood that allthe terms used herein are descriptive rather than limiting, and thatmany changes, modifications, and substitutions can be made by one havingskill in the art without departing from the spirit and scope of theclaims below.

What is claimed is:
 1. A dual dosage capsule, comprising: a firstcapsule member comprising a first fill material and having a closed endand an open end sealed by a first cap; a second capsule membercomprising a second fill material and having a closed end and an openend sealed by a second cap; and an annular band having a first endconnected to the open end of the first capsule member to sealinglycontain the first fill material in the first capsule member with thefirst cap and an opposing second end connected to the open end of thesecond capsule member to sealingly contain the second fill material inthe second capsule member with the second cap, thereby defining aninternal chamber between the first cap and the second cap within theannular band: wherein the annular band comprises one or more aperturestherethrough radially oriented relative to a longitudinal axis of thecapsule, wherein the internal chamber is empty thereby placing theinternal chamber, the first cap, and the second cap in fluidcommunication with the environment outside the capsule.
 2. The dualdosage capsule of claim 1, wherein the open end of the first capsulemember is received in the first end of the annular band and is sealed bythe first cap, and the open end of the second capsule member is receivedin the second end of the annular band and is sealed by the second cap;or the first end of the annular band is received in the open end of thefirst capsule member which is sealed by the first cap, and the secondend of the annular band is received in the open end of the secondcapsule member which is sealed by the first cap.
 3. The dual dosagecapsule of claim 2, wherein the open end of the first capsule member isreceived in the first end of the annular band, and the first cap isseated within the annular band sealingly closing the open end of thefirst capsule member.
 4. The dual dosage capsule of claim 3, wherein theopen end of the second capsule member is received in the second end ofthe annular band, and the second cap is seated within the annular bandsealingly closing the open end of the second capsule member.
 5. The dualdosage capsule of claim 3, wherein the annular band comprises the secondcap for sealingly closing the open end of the second capsule member. 6.The dual dosage capsule of claim 2, wherein the annular band comprises afirst annular band portion having the first cap integral therewith and asecond annular band portion having the second cap integral therewith,wherein the first annular band portion and the second annular bandportion each have an open end opposite the caps therein and the openends are connectable to one another to form the annular band and theinternal chamber.
 7. The dual dosage capsule of claim 6, wherein thefirst annular band portion and/or the second annular band portioncomprise a plurality of apertures therethrough radially orientedrelative to a longitudinal axis of the capsule, thereby placing theinternal chamber in fluid communication with the environment outside thecapsule.
 8. The dual dosage capsule of claim 2, wherein the annular bandcomprises the first cap for the first capsule member therein and thesecond cap for the second capsule member therein defining the internalchamber therebetween.
 9. The dual dosage capsule of claim 1, wherein thefirst fill material and the second fill material are the same ordifferent.
 10. The dual dosage capsule of claim 9, wherein the firstfill material and/or the second fill material comprise an activeingredient.
 11. The dual dosage capsule of claim 1, wherein the firstcap comprises a rapidly dissolving composition.
 12. The dual dosagecapsule of claim 1, wherein the first cap comprises a very rapidlydissolving composition.
 13. The dual dosage capsule of claim 1, whereinthe first cap and/or first capsule member dissolves while in theintestine.
 14. The dual dosage capsule of claim 1, wherein the firstcapsule member comprises a rapidly dissolving composition and the secondcapsule member comprises a composition that dissolves slower than thefirst capsule member.
 15. A method of providing a dual release of one ormore active ingredients, the method comprising: exposing a dual releasedosage form capsule of claim 1 to a fluid; wherein exposure of the dualrelease dosage form capsule to the fluid is associated with a firstrelease of at least a portion of the first fill material from the dualrelease dosage form capsule before a second release of at least aportion of the second fill material, and the first fill material and/orthe second fill material comprise an active ingredient.
 16. A method ofproviding a dual release of one or more active ingredients in a subject,the method comprising: administering to the subject the dual releasedosage form capsule of claim 1; wherein administration of the dualrelease dosage form capsule results in a first release of at least aportion of the first fill material from the dual release dosage formcapsule before a second release of at least a portion of the second fillmaterial, and the first fill material and/or the second fill materialcomprise an active ingredient.
 17. The method of claim 16, wherein thesecond release occurs at least one hour after the first release.
 18. Themethod of any of claim 16, wherein the first or second fill materialcomprises a probiotic or a prebiotic.
 19. The method of claim 16,wherein administering comprises orally ingesting the dual release dosagecapsule.